Triple Immunotherapy Overcomes Immune Evasion by Tumor in a Melanoma Mouse Model.

Background: Melanoma is a malignancy with increasing incidence that underlies most skin cancer-related deaths. Advanced melanoma patients still have poor prognosis despite recently developed immunotherapies. This study devises a triple immunotherapy to treat melanoma in a mouse model. The combination includes anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4) antibodies, Monophosphoryl-lipid-A (MPLA), and an Indolamine-Dioxygenase-1 (IDO1) inhibitor. The aim of the study is, first, to rule out any major toxic effects related to this therapy and, second, to assess its antitumor effects. Methods: Cancer-free C57BL/6 mice were randomized into control groups and groups receiving single, dual, or triple therapies of the defined treatments. Clinical signs, weight gain, and histological sections from their main organs were assessed. Then, melanoma-bearing mice were segregated into similar groups, monitored for survival, and their tumor size was measured repeatedly. Finally, flow cytometry was used to analyze immune cell populations in the tumor masses including CD4+, CD8+, and regulatory T cells in addition to natural killer cells. Results: No adverse effects were detected in any of the treated groups. Survival analysis indicated that the groups receiving dual or triple therapies had prolonged survival compared to the controls. However, the group receiving triple therapy was the only group to show statistically significant increase in survival compared to the controls. Tumor size progression paralleled the survival outcome. The group receiving the triple therapy showed statistically significant smaller tumor sizes compared to all the other groups throughout the whole monitoring period. Flow cytometry used to analyze immune cell populations in the tumor mass indicated that the triple immune therapy was capable of significantly enhancing the natural killer cell counts as well as the CD3+CD4+/Treg and CD3+CD8+/Treg ratios possibly enhancing the anti-tumorigenic environment. Conclusions: Generated data rule out any major adverse events pertaining to the triple immunotherapy and reveal its enhanced effectiveness in thwarting melanoma progression over all other tested treatments.

Atorvastatin increases the production of proinflammatory cytokines and decreases the survival of Escherichia coli-infected mice.

To assess whether the immunosuppressive effects of atorvastatin outweigh its antibacterial ones in an infection, mice were infected with Escherichia coli and administered atorvastatin; survival rates were then monitored. Mice treated with atorvastatin post-infection showed a remarkable decrease in their survival rate. On the other hand, the higher the level of serum IFN-γ in the infected mice treated with atorvastatin, the lower was the survival rate. Levels of IL-4 were markedly depressed in all groups infected with E. coli and treated with atorvastatin. Since atorvastatin inhibits IFN-γ expression in the absence of bacterial infection, we examined whether bacterial lipopolysaccharide (LPS) was the element capable of overriding this inhibition. Mouse peripheral blood mononuclear cells were treated with atorvastatin and lipopolysaccharide ex vivo then proinflammatory (IFN-γ, TNFα, IL-6) and prohumoral/regulatory (IL-4, IL-13, IL-10) cytokine levels were analyzed in culture supernatants. While proinflammatory cytokine levels were decreased upon treatment with atorvastatin alone, their levels were markedly elevated by treatment with LPS, bacterial lysate or bacterial culture supernatant. On the other hand, atorvastatin exerted an inhibitory effect on production of the prohumoral/regulatory cytokines. Our data indicates that any consideration for statins as antimicrobial treatment should assess the possible adverse outcomes.

Epstein-Barr virus DNA modulates regulatory T-cell programming in addition to enhancing interleukin-17A production via Toll-like receptor 9.

Infection with the Epstein-Barr virus (EBV) has been associated with several autoimmune diseases including rheumatoid arthritis (RA). We have previously reported that DNA from this virus enhances production of the pro-autoimmune interleukin 17A (IL-17A) in mice. In this study we assessed the effect of EBV DNA on regulatory T cell programming and examined whether it mediated its effects via Toll-like receptor 9 (TLR9) in mice; moreover, we evaluated whether EBV DNA in humans had similar effects to those seen in mice. For this purpose, we assessed the linearity of the correlation between EBV DNA and IL-17A levels in RA subjects and matched controls. A modulatory effect for the viral DNA was observed for regulatory T cell markers with an inhibitory effect observed for CTLA4 expression in the EBV DNA-treated mice. To examine whether TLR9 mediated the detection of EBV DNA and enhancement of IL-17A production, mouse peripheral blood mononuclear cells were treated with the DNA in the presence or absence of the TLR9 inhibitor ODN 2088. Subsequently, IL-17A production from these cells was assessed. Treatment with the TLR9 inhibitor resulted in a significant decrease in IL-17A production indicating that TLR9 is involved in this pathway. In human subjects, examining the linearity of the correlation between EBV DNA and IL-17A levels in RA subjects showed a propensity for linearity that was not observed in controls. Our data thus indicates that EBV DNA itself acts as a modulator of the Th17 compartment as well as that of regulatory T cell mechanisms. The involvement of TLR9 in the EBV DNA-triggered induction of IL-17A suggests therapeutic targeting of this endosomal receptor in EBV positive subjects with an autoimmune flare-up or possibly for prophylactic purposes.

The Effect of Denatured Flagellin on Toll-Like Receptor-5 (TLR-5) in Mice.

BACKGROUND: Previous studies have demonstrated that flagellin, a component of bacterial flagella, engages Toll-Like receptor 5 (TLR-5) causing the activation of the Myeloid Differentiation Factor-88 (MYD-88) pathway that leads to the production of pro-inflammatory cytokines including Tumor Necrosis Factor-alpha (TNF-α) and Interleukin-12 (IL-12). In physiological levels, cytokines can aid in protection against infectious agents. However, excessive production of cytokines can lead to septic shock during sepsis. OBJECTIVE: In this study, we aimed at investigating the effect of denatured flagellin on hindering the effects induced by intact flagellin or flagellated Pseudomonas aeruginosa on the Toll-Like Receptor-5 (TLR-5) in mice. METHODS: Mouse mononuclear cells (MNCs) were cultured with intact flagellin, heat-denatured flagellin, TLR-5 antagonist, Pseudomonas aeruginosa, and TLR-4 antagonist each alone or in combinations. Supernatants were collected at 4 hours post incubation to assess the levels of IL-12 and TNF-α by Enzyme-Linked ImmunoAssay (ELISA). Furthermore, groups of BALB/c mice were injected intraperitoneally (IP) with Pseudomonas aeruginosa, LPS-RS, intact flagellin, and denatured flagellin, each alone or in different combinations. Serum levels of IL-12 and TNF-α were measured at 2, 4, and 6 hours post injections of Pseudomonas aeruginosa or intact flagellin. RESULTS: Pretreatment with denatured flagellin significantly reduced the amount of TNF-α and IL-12 produced both in vitro and in vivo by intact flagellin or Pseudomonas aeruginosa. CONCLUSION: Denatured flagellin suppressed the production of the pro-inflammatory cytokines induced by intact flagellin or Pseudomonas aeruginosa both in vitro and in vivo, probably by blocking TLR5. Denatured flagellin might be considered as an anti-septic shock agent.

Epstein-Barr Virus and Human herpes virus 6 Type A DNA Enhance IL-17 Production in Mice.

Several studies have shown a potential association between the Herpesviridae members, the Epstein-Barr virus (EBV) and Human herpes virus 6 (HHV-6), and an increased risk of autoimmune disease development. Because of the ability of these viruses to cause recurrent infections, various viral antigens, including viral DNA, are consistently shed. These antigens may then play a role in triggering autoimmune processes or contributing to autoimmune mechanisms. Therefore, this study examined whether the DNA of EBV or that of HHV-6A is capable of triggering IL-17, the autoimmune-associated cytokine, in mice. BALB/c mice were intraperitoneally injected with various copy numbers of either EBV or HHV-6A DNA. One group was injected with sterile water (the DNA solvent), and another was left uninjected. A mouse group that was administered DNA obtained from Staphylococcus epidermidis was included to ensure that any observed effects would pertain to the viral DNA tested. Mice were sacrificed and their sera were examined using an enzyme-linked immunosorbent assay for IL-17 and IL-23, as pro-autoimmune cytokines, IL-10, as an anti-inflammatory cytokine, and IFN-γ, as a pro-inflammatory cytokine, on days 3, 6, and 9 post-injection. All mouse groups injected with different copy numbers of EBV DNA or HHV-6A DNA displayed higher IL-17 levels than did the group injected with water on days 3, 6, and 9 post-injection. The highest IL-17 levels appeared to coincide with a marked increase in IL-23 and a decrease in IL-10 levels. Unlike the S. epidermidis DNA, which increased IFN-γ levels but not IL-17 or IL-23 levels, the viral DNA tested increased all three mediators, indicating that triggering Th17 responses is a specific property of EBV and HHV-6A DNA. In conclusion, EBV and HHV-6A viral DNA are capable of enhancing the production of the pro-inflammatory cytokine IL-17, which has been shown to play a role in autoimmune diseases.

Atorvastatin Reduces the Survival of Candida albicans-Infected BALB/c Mice.

Several antimicrobial and immunosuppressive effects have been attributed to the statins class of antihyperlipidemia drugs. Several studies have also indicated clinical benefits for the use of statins during the management of infections and sepsis. To assess whether the immunosuppressive effects of statins outweigh their antimicrobial effects during a fungal infection BALB/c mice were administered Candida albicans via intraperitoneal injection. These mice received either a co-injection of atorvastatin along with the infection, were treated with one injection of atorvastatin per day for 5 days prior to infection, or were infected and then treated with one injection of atorvastatin for 5 days afterward. Groups that received C. albicans without being treated with atorvastatin were included as controls along with a group that only received phosphate-buffered saline. Mouse survival was then monitored; additionally, serum IFN-γ and IL-4 levels were determined by enzyme linked immunosorbent assay to assess pro-inflammatory and pro-humoral responses, respectively. Atorvastatin administration was capable of altering mouse survival rate with the lowest rate (11.1%) being observed in the group treated for 5 days prior to infection with atorvastatin compared to mice infected but not treated with atorvastatin (44.4%). IFN-γ and IL-4 levels were depressed in all C. albicans-infected groups treated with atorvastatin. The possibility that statin administration may suppress or modulate particular components of the immune system during an infection in man should be further explored in large randomized controlled trials.

Effects of catalase and 1400W on the number of interleukin-4 and interferon-γ secreting spleen cells in mice injected with ovalbumin and alum.

CONTEXT: Alum is thought to induce inflammation resulting in the release of danger signals such as uric acid (UA) which in turn enhances the immune response to an antigen. Hydrogen peroxide (H(2)O(2)) is produced as a byproduct in the purine catabolic pathway that leads to the production of UA. In addition, serum nitric oxide (NO) levels are increased in inflammation. OBJECTIVE: To further explore the mechanism of action of alum, this study was designed to determine the effects of catalase and 1400W on the number of interleukin-4 (IL-4) and interferon-γ (IFN-γ) secreting spleen cells in mice given ovalbumin (OVA) with alum. MATERIALS AND METHODS: Groups of BALB/c mice were injected intraperitoneally with alum + OVA, alum, OVA, catalase, or 1400W. Other groups were treated with catalase or 1400W and given alum + OVA. The number of IL-4 and IFN-γ secreting spleen cells were determined at days 4 and 7 postinjection by enzyme-linked immunosorbent spot (ELISPOT). RESULTS: Catalase and 1400W caused a decrease in the number of IL-4 secreting spleen cells induced by alum + OVA. 1400W caused a decline in the IFN-γ secreting spleen cells induced by alum + OVA. Catalase caused an increase in IFN-γ secreting spleen cells. DISCUSSION AND CONCLUSION: It appears that H(2)O(2) and NO are needed for alum-induced production of a T-helper 2 cytokine. NO also appears to be needed, whereas H(2)O(2) appeared to inhibit an alum-induced production of a T-helper 1 cytokine. These results might explain why alum is mainly a promoter of a T-helper 2 response.

The impact of prophylactic antiviral agents and statin administration on graft longevity in kidney allograft recipients.

CONTEXT: In an earlier study, we compared the duration of kidney graft survival between two groups of recipients; one on triple (cyclosporine, prednisone and mycophenolate mofetil) and the other on quadruple (cyclosporine, prednisone, mycophenolate mofetil, and sirolimus) immunosuppressive therapy. OBJECTIVE: The aim of this study was to examine the impact of antiviral and statin therapy on graft longevity. MATERIALS AND METHODS: One hundred five kidney allograft recipients were preoperatively assessed for serological markers of infection with various viral agents. All patients were on a prophylactic antiviral regimen of acyclovir and gancyclovir. Seventeen patients were on a statin. Patients were monitored for viral infections and graft rejection or loss for period of 3 years posttransplantation. RESULTS: We detected a high preoperative prevalence rate of IgG immunoglobulins versus the latency-establishing Herpesviridae viruses. Two patients who were preoperatively IgG positive for CMV had cytomegalovirus disease after transplantation. One patient who was preoperatively IgG positive for VZV had shingles after the surgery. No other confirmed viral infections were reported. Thirteen of 88 patients (14.77%) whose treatment regimen did not include a statin suffered a rejection episode or lost the graft whereas 1 of 17 patients (5.88%) on a statin had a rejection episode. CONCLUSIONS: The low rate of viral infections observed in our study population supports the utility of prophylactic administration of antiviral agents to transplant recipients. However, statins seem to have a protective effect on graft longevity (odds ratio [OR] = 0.361, 95% confidence interval [CI] = 0.044-2.957).

Laparoscopic donor nephrectomy: The Middle East experience.

OBJECTIVES: To summarize the experience of the Middle East in laparoscopic donor nephrectomy (LDN), to discuss the associated advantages and salient problems, to examine the learning curve encountered compared with that of the pioneering centres in the West, and the contribution of the regional centres to the worldwide experience. METHODS: We searched Medline and PubMed for all centres performing LDN in the Middle East. Questionnaires were e-mailed to the regional transplantation centres, and programme directors, and leading urological and transplant surgeons were contacted by telephone. RESULTS: LDN in the Middle East was first introduced in 2000; this approach has been pioneered and practised at seven transplant centres within five countries in the region, and was restricted to only three Arab countries, i.e. Lebanon, Egypt and Kuwait. Data collection yielded a total of 888 procedures over one decade, representing only 2% of the total of ≈50,000 transplants during the same period. Despite variability of accurate reporting the overall outcomes were similar to those of open DN. The spectrum of complications was comparable to that from major centres in the USA during their learning curve. CONCLUSIONS: The introduction of LDN in the Middle East has been gratifying. The relative hesitancy in introducing LDN in the rest of the Arab Middle East is multifaceted. The advantages conferred to the donor underscore the need for further expansion of this approach for kidney retrieval.

Identification and antibacterial resistance of bacteria isolated from poultry.

Food-borne infections are among the prominent health hazards. Antibacterial agents (ABA) are usually administered to poultry in Lebanon as antibiotic growth promoters (AGP), which might lead to the dissemination of resistant bacterial strains. The aims of this study were to isolate potential food borne pathogens from poultry and investigate an association between AGP usage and antibacterial resistance (ABR). Isolates were obtained from the culture of cloacae swabs and identified. Escherichia coli was the predominant isolate. There was a significant association between the use of tetracycline and gentamicin as AGP and the number of E. coli isolates resistant to these ABA.

Decrease in Shiga toxin expression using a minimal inhibitory concentration of rifampicin followed by bactericidal gentamicin treatment enhances survival of Escherichia coli O157:H7-infected BALB/c mice.

BACKGROUND: Treatment of Escherichia coli O157:H7 infections with antimicrobial agents is controversial due to an association with potentially fatal sequelae. The production of Shiga toxins is believed to be central to the pathogenesis of this organism. Therefore, decreasing the expression of these toxins prior to bacterial eradication may provide a safer course of therapy. METHODS: The utility of decreasing Shiga toxin gene expression in E. coli O157:H7 with rifampicin prior to bacterial eradication with gentamicin was evaluated in vitro using real-time reverse-transcription polymerase chain reaction. Toxin release from treated bacterial cells was assayed for with reverse passive latex agglutination. The effect of this treatment on the survival of E. coli O157:H7-infected BALB/c mice was also monitored. RESULTS: Transcription of Shiga toxin-encoding genes was considerably decreased as an effect of treating E. coli O157:H7 in vitro with the minimum inhibitory concentration (MIC) of rifampicin followed by the minimum bactericidal concentration (MBC) of gentamicin (> 99% decrease) compared to treatment with gentamicin alone (50-75% decrease). The release of Shiga toxins from E. coli O157:H7 incubated with the MIC of rifampicin followed by addition of the MBC of gentamicin was decreased as well. On the other hand, the highest survival rate in BALB/c mice infected with E. coli O157:H7 was observed in those treated with the in vivo MIC equivalent dose of rifampicin followed by the in vivo MBC equivalent dose of gentamicin compared to mice treated with gentamicin or rifampicin alone. CONCLUSIONS: The use of non-lethal expression-inhibitory doses of antimicrobial agents prior to bactericidal ones in treating E. coli O157:H7 infection is effective and may be potentially useful in human infections with this agent in addition to other Shiga toxin producing E. coli strains.

Identification of bacteria isolated from nasal polyps and their ability to produce superantigens and biofilms in Lebanese patients.

Staphylococcus aureus superantigens and bacterial biofilms have been implicated in the development of chronic rhinosinusitis and nasal polyps. We conducted a study of 32 Lebanese patients-21 males and 11 females, aged 15 to 71 years (mean: 39)-to identify bacteria isolated from nasal polyps and to determine if these bacteria produced superantigens and biofilms. Polyps were surgically removed, homogenized, and subjected to bacteriologic studies. The presence or absence of S aureus enterotoxin A, B, C, and D (superantigen) genes was determined in all isolates by polymerase chain reaction. Biofilm production by coagulase-negative staphylococci and Pseudomonas aeruginosa was assessed by tissue culture plate assay. A total of 34 bacterial species/groups were isolated from the nasal polyps. Of these, only 3 (8.8%) were S aureus, and only 1 possessed an enterotoxin-coding gene (enterotoxin B). Moreover, of the 21 coagulase-negative staphylococci isolates that were found, none possessed the investigated genes, and only 1 had a strong biofilm-formation property. Our results could not confirm that S aureus enterotoxins (superantigens) or biofilm-producing bacteria play a role in the development of nasal polyps in the Lebanese group studied.

The effect of five antibacterial agents on the physiological levels of serum nitric oxide in mice.

In addition to their action on microorganisms, antibacterial agents have been reported to affect host defense mechanisms. Nitric oxide (NO) that is produced by a number of cell types in the innate immune response is bactericidal, but when produced in excessive amounts it could be detrimental to the host. In this study, five antibacterial agents (gentamicin, tobramycin, imipenem, tigecycline, isoniazid) were compared with respect to their ability to affect NO production in mice. Groups of mice were injected with the different antibacterial agents, and at different time intervals post-injection serum NO levels were determined using the Griess reagent. All the antibacterial agents tested showed a significant effect in reducing NO levels in mice. It could be hypothesized that the excessive production of NO in infectious diseases is in most instances suppressed by the antibacterial agent(s) used.

Role of rifampicin in limiting Escherichia coli O157:H7 Shiga-like toxin expression and enhancement of survival of infected BALB/c mice.

The sequelae of infection with Escherichia coli O157:H7 include the potentially fatal haemolytic uraemic syndrome. The pathobiological process of E. coli O157:H7 is chiefly dependent on the production of Shiga-like toxins I and II (SLT-I and -II). Antibiotic treatment is currently refrained from since it may lead to enhanced release of SLTs from the bacterium. In this study, the potential utility of rifampicin in treating E. coli O157:H7 infections was assessed both in vitro and in vivo. Five strains of E. coli O157:H7 were tested by reverse transcriptase polymerase chain reaction (RT-PCR) for the transcription of the SLT-I- and SLT-II-encoding genes (stx1 and stx2, respectively). Treatment of bacterial strains with the rifampicin minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC), or the MIC followed by the MBC led to the inhibition of stx1 and stx2 gene transcription. Treatment with the MIC or with the MIC followed by the MBC was also capable of limiting toxin release. SLT-I and SLT-II detection by reverse passive latex agglutination showed an effective decrease in toxin titres following treatment with the MIC of rifampicin or with the MIC followed by the MBC. Treatment of cultures with the MBC alone was not as effective in decreasing toxin titres. The efficacy of rifampicin in treating E. coli O157:H7-infected BALB/c mice was also assessed. Rifampicin treatment resulted in enhanced mouse survival and limited the weight loss of infected animals. In conclusion, both in vitro and in vivo tests showed that rifampicin may be useful in treating E. coli O157:H7 infection.

Monoclonal antibodies used as prophylactic, therapeutic and diagnostic agents.

Monoclonal antibodies can be of mouse, part mouse part human (chimeric, humanized), or of human origin. Their preparation involves hybridoma, gene cloning, gene recombination, phage display, and gene transfection techniques. The preparation, mechanism of action, uses, and possible adverse effects of most of the available monoclonal antibodies used as prophylactic, therapeutic, and diagnostic agents are reviewed.

Patented small molecules against psoriasis.

BACKGROUND: It is hypothesized that psoriasis is an autoimmune disease. The most recent therapeutic approach that proved to be more effective than earlier methods of treatment is the use of mAb/fusion proteins. Efforts nowadays are focused on investigating the antipsoriatic affect of small molecules that can be administered orally, some of which are capable of entering cells, and being selective in targeting intracellular pathways. OBJECTIVE: Preclinical patented small molecules that are recommended for the treatment of psoriasis are reviewed. Emphasis is placed on their mechanism of action. METHODS: http://ep.espacenet.com/ , Pubmed, Scopus and Google websites were the main sources used for the patented small molecule search. A number of patents were poorly described and difficulties were faced in trying to figure out the patentee(s) explanation. Moreover, most patents were recommended for the treatment of a number of autoimmune diseases and cancer, and not only for psoriasis. RESULTS/CONCLUSIONS: Small molecules that inhibit the activation of T lymphocytes, leukocyte trafficking, leukotriene activity/production and angiogenesis, and promote apoptosis have been patented. Small molecules that have been patented for the treatment of other autoimmune diseases and could be used for treating psoriasis are described. Moreover, other possible mechanistic approaches using small molecules are discussed.

The potential use of Toll-like receptor (TLR) agonists and antagonists as prophylactic and/or therapeutic agents.

Toll-like receptors (TLR) and their ligands are one of the main players in the initiation of innate immunity which precedes, and is required, for the establishment of adaptive immunity. Manipulating the immune response by using TLR agonists or antagonists might be of therapeutic and/or prophylactic value. This review covers; 1-TLR. their natural ligands and ligand - TLR signaling events, 2-TLR against and their use in clinical trials as vaccine adjuvants, and to treat allergy, cancer and infectious diseases, 3-TLR antagonists and their use in clinical trials to treat septic shock and autoimmune diseases. Potential drawbacks related to their potential use as prophylactic and/or therapeutic agents are discussed.

Influence of HLA disparity, immunosuppressive regimen used, and type of kidney allograft on production of anti-HLA class-I antibodies after transplant and occurrence of rejection.

We studied the effects of HLA disparity, immunosuppressive regimen used, and the type of kidney allograft on production of anti-HLA antibodies after transplant and the occurrence of rejection episodes. Five living-unrelated donors and 4 living-related donors kidney recipients received quadruple therapy (including sirolimus and mycophenolate mofetil). Fifteen living-unrelated donors and 19 living-related donors received triple therapy (excluding sirolimus). A single bolus of 4 to 6 mg/kg rabbit anti-human T-lymphocyte immune serum was included with both regimens. Recipients were studied over a 3-year period. Human leukocyte antigen profiles were determined by DNA (SSP) typing, and anti-HLA class-I antibodies were determined by the complement-dependent microcytotoxicity assay and an enzyme-linked immunosorbent assay. The degree of HLA disparity did not appear to affect anti-HLA antibody production or the occurrences of rejection episodes. None of the patients who received quadruple therapy developed anti-HLA class-I antibodies. Two living-unrelated donors and 2 living-related donors recipients who received triple therapy developed anti-HLA class-I antibodies. One of the 2 living-unrelated donors antibody-positive patients rejected the kidney and returned to dialysis, and the other patient has normal graft function 3 years after the transplant. The 2 living-related donors patients with normal graft function were antibody-positive 1 year after the transplant but were antibody-negative at 2 and 3 years after transplant. Sirolimus appeared to inhibit production of antibodies after transplant. Moreover, use of present day immunosuppressive agents diminishes the role of HLA matching in relation to the occurrence of rejection episodes.

The effects of Alcea rosea L., Malva sylvestris L. and Salvia libanotica L. water extracts on the production of anti-egg albumin antibodies, interleukin-4, gamma interferon and interleukin-12 in BALB/c mice.

Polysaccharides obtained from certain plants have been reported to have immunomodulatory properties. As a consequence of these reports the aim of this study was to investigate some immunomodulatory properties of water extracts of Alcea rosea L. (ARE), Malva sylvestris L. (MSE) and Salvia libanotica L. (SLE).Groups of egg albumin (EA)-immunized and -non-immunized Balb/c mice were treated with the carbohydrate-rich water extracts. Mice from each group were bled and their spleens removed at 3, 6 and 10 days post-immunization/treatment. Anti-egg albumin antibody levels in the processed sera were determined by an enzyme linked immunosorbent assay (ELISA). RNA was extracted from spleen cells and interleukin-4 (IL-4), interleukin-12 (IL-12) and gamma-interferon transcripts were determined by the reverse transcription polymerase chain reaction (RT-PCR).ARE appeared to boost the antibody response to EA, but had no effect on IL-4 and gamma-interferon gene transcription. MSE and SLE appeared to have no effect on anti-EA antibody production, but enhanced IL-12 and gamma-interferon gene transcription. MSE appeared to switch off, and SLE had no effect on, IL-4 transcription.In conclusion, it appears that ARE is a B-lymphocyte polyclonal activator, and MSE and SLE are macrophage and T helper-1 (Th-1) activators.

Streptococcus sp. and Staphylococcus aureus isolates from patients with psoriasis possess genes that code for toxins (superantigens): clinical and therapeutic implications.

Superantigens are powerful T lymphocyte-stimulating agents that are believed to contribute to the pathogenesis of certain diseases such as psoriasis. Toxins produced by Streptococcus pyogenes and Staphylococcus aureus are superantigens. The aim of this study was to detect genes that code for superantigens in Streptococcus and Staphylococcus aureus isolates from psoriatic patients. Primers to amplify streptococcal pyrogenic exotoxin A, B, and C and streptolysin O genes and staphylococcal enterotoxin A, B, C, and D genes were used. Streptococcal exotoxin B was detected in five streptococcal isolates. Staphyloccocus aureus enterotoxin A and/or C genes were detected in nine S. aureus isolates. Isolates from 13 of 22 patients possesed gene(s) that code for toxin(s) (superantigens). These results might support the role of superantigens in the exacerbation of psoriasis.