Immunogenicity of pneumococcal polysaccharide vaccine in adult systemic lupus erythematosus patients undergoing immunosuppressive treatment.

OBJECTIVE: To evaluate the immunogenicity of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in adult systemic lupus erythematosus patients undergoing (IS group) and not undergoing (non-IS group) immunosuppressive treatment. METHODS: In this prospective open-label study from February 2013 to April 2014, 54 patients had blood samples collected immediately before PPSV23 immunization and 4-6 weeks thereafter for the ELISA measurement of IgG antibody levels against seven pneumococcal serotypes. Positive vaccine response for each serotype was defined as a four-fold or greater antibody response over baseline levels or as a post-vaccine anti-pneumococcal IgG level ≥1.3 µg/ml when baseline values were <1.3 µg/ml. Patients should have responded appropriately to ≥70% of the tested serotypes. We also calculated the mean ratio of post- to pre-vaccination anti-pneumococcal IgG levels. RESULTS: Twenty-eight patients were classified into the IS group and 26 into non-IS group. The median dose of prednisone at baseline was ≤5 mg/day in both groups. Serotype-specific vaccine response rates were not significantly different between the groups. Less than 40% of patients responded adequately by both vaccine response criteria, being numerically lower among IS patients. The mean ratio of increase in anti-pneumococcal levels was 6.4 versus 4.7 (p = 0.001) in non-IS and IS groups, respectively. CONCLUSION: The vaccine was poorly immunogenic, especially among adult systemic lupus erythematosus patients under immunosuppressive therapy.

Are women with lupus at higher risk of HPV infection?

Human papillomavirus (HPV) is the etiological agent of cervical cancer, the second most prevalent neoplasia among women. Although it has been proven that systemic lupus erythematosus (SLE) patients have higher frequency of cervical dysplasia, few studies have focused on HPV prevalence among them. This study aimed to investigate HPV prevalence among SLE patients and to evaluate associated risk factors, including the use of immunosuppressors (IM). Total DNA extracted from cervical samples of 173 SLE patients and 217 women (control group) submitted to routine cervical cytopathology was used as template in polymerase chain reaction (PCR)-based assays for detection of HPV DNA. HPV genotyping was performed by type-specific PCR, PCR-RFLP and/or DNA sequencing. Statistical methods included univariate analysis and logistic regression. Despite presenting significantly fewer HPV risk factors, SLE patients were found to have a threefold increase in HPV infection, mostly genotypes 53, 58, 45, 66, 6, 84, 83, 61, as compared with controls, who presented types 6, 18 and 61 more frequently. The higher rate of HPV infection was associated with immunosuppressive therapy. This study provides evidence that SLE patients have a high prevalence of HPV infection, which is even higher with the use of IM, a condition that might necessitate a more frequent cervical cancer screening program for these women.

Serum vascular endothelial growth factor in late rheumatoid arthritis.

OBJECTIVES: To investigate the serum levels of VEGF in patients with rheumatoid arthritis of long duration. METHODS: Serum VEGF levels were measured in 118 patients with long-standing rheumatoid arthritis according to the ACR criteria (mean duration 12 years). The disease activity score was evaluated by the method of van der Heijde et al. RESULTS: Serum levels of VEGF in patients with RA were significantly higher than in healthy controls. VEGF levels showed no correlation with CRP, SAA amyloid protein, or the disease activity score. CONCLUSIONS: Our findings suggest that, contrary to the results reported in patients with early onset RA, where VEGF appears to play an active part in joint inflammation, in long-standing RA elevated VEGF serum levels may be an independent marker although its significance remain to be established.

In vitro and in vivo toxicological study of the Pterodon pubescens seed oil.

The oil of Pterodon pubescens seeds (PpSO) is known for its cercaricidal and anti-inflammatory effects. Its anti-rheumatic activity was recently reported using mice with collagen II-induced arthritis treated with a hydroalcoholic extract of PpSO, mimicking the wine infusion used in popular medicine. In the present study, PpSO was tested for acute toxicity, mutagenic activity and cytotoxicity for human peripheral blood mononuclear cells (PBMNC). PpSO was obtained after seed extraction with 100% ethanol and evaporation. Cytotoxicity was estimated using the tetrazolium salt reduction test (MTT assay) by PBMNC (2.5 x 10(5) cells/ml) after exposure to 0.07, 0.7 and 7 microg PpSO/ml for 24 and 48 h. In the mutagenesis assay, the Salmonella/mammalian microsome assay was employed with or without metabolization. Acute toxicity was studied on 30 (n = 10/group) male DBA1/J mice (20 +/- 2 g) after a single oral dose of 2, 4, and 8 g PpSO/kg b.w. The animals were observed for 24 h, anesthetized, sacrificed and autopsied. The organs were processed for histopathology by staining with hematoxylin-eosin. The IC50 of PpSO to PBMNC in RPMI 1640 supplemented with 5% fetal calf serum (FCS) was 2 and 1 microg PpSO/ml after 24 and 48 h, respectively. The mutagenic test performed with or without metabolic activation of PpSO did not show mutagenic activity for the concentrations tested (7 and 70 microg/ml). Mouse mortality or significant signs of acute toxicity (ocular, cardiovascular, gastrointestinal, motor or respiratory signs) for the PpSO doses tested was not observed. The organs did not show any macroscopic alterations. Histopathologic analysis of the tissues also did not demonstrate any lesions. The present study provides data to classify PpSO as non-cytotoxic to PBMNC, non-mutagenic, and non-toxic after acute administration since the PpSO doses tested were extremely higher than those used by the population.

Anti-arthritic effect and subacute toxicological evaluation of Baccharis genistelloides aqueous extract.

This work studies the potential subacute toxicological effects of the aqueous extract of Baccharis genistelloides (AEBg) and demonstrates a new anti-arthritic therapeutic effect. The treatment of the collagen-induced arthritis (CIA) group with 4.2 mg/kg AEBg induced an important decrease (75%) in CIA severity in all animals, while the 42 mg/kg dose treated only 50% of animals. After AEBg treatment, no significant differences were observed in body weight, aspect, color and relative weight of liver, kidneys, thymus or lungs between CIA groups. CIA and healthy AEBg groups treated with both doses did not show genotoxic effects to liver and kidney cells by the Comet assay, compared to its own control group. The augmented AST in the CIA group, compared to healthy control one was regularized by the AEBg treatment with 4.2 mg/kg but not with 42 mg/kg. No other significant difference was found on serum biochemical parameters, as well as on spontaneous or stimulated lymphocyte proliferation between CIA groups. The treatment of healthy animals with AEBg 4.2 mg/kg did not change the aspect, color or relative weight of kidneys, liver or lungs but reduced the body weight, the thymus and popliteal lymph node (PLN) relative weight and serum glucose and triglyceride levels. Concluding, our results indicate an anti-arthritic effects of AEBg without liver and kidney subacute toxicity and hypoglycemic and hypotriglyceridemic actions on healthy animals.

Acute and topic anti-edematogenic fractions isolated from the seeds of Pterodon pubescens.

We previously demonstrated that alcoholic extracts from Pterodon pubescens Benth. (Sucupira branca, Leguminosae) seeds exhibit anti-arthritic activity. In the present work we show that the oleaginous extract obtained from P. pubescens seeds (OEP) exhibits acute or topic anti-edematogenic activity when tested in carrageenan-induced paw edema or in croton oil-induced ear edema assays, respectively. Four fractions were obtained from OEP by sequential liquid-liquid extraction. The anti-edematogenic properties were predominant in the hexanic fraction, which was further fractionated by HPLC, yielding three sub-fractions (PF1.1, PF1.2 and PF1.3). PF1.1 and PF1.3 showed potent acute and topic anti-edematogenic activity. The PF1.2 sub-fraction, although not active in the carrageenan assay, exhibited a potent anti-edematogenic activity in the croton oil-induced ear edema. This sub-fraction shows a maximum efficacy similar to indometacin in a lower dose. The PF1.1 sub-fraction presented a complex mixture containing furane diterpene derivatives of vouacapan. PF1.2 consists of a single substance, geranylgeraniol, as determined by GC/MS and NMR, while PF1.3 contains farnesol.

Subacute toxicity evaluation of a hydroalcoholic extract of Pterodon pubescens seeds in mice with collagen-induced arthritis.

When the immune system is stimulated there is a concomitant decrease in drug biotransformation and elimination that may results in unwanted drug response and toxic side effects. We investigated the subacute toxicity of a hydroalcoholic extract of Pterodon pubescens seeds (HEPp) to DBA1/J mice with collagen II-induced arthritis. The oral treatment with HEPp reduced the arthritic index without any concomitant alteration in their hematological examination, histopathological analysis and relative or absolute weight of several organs and in several clinical biochemical parameters when compared with the control group. We concluded that daily administration of anti-arthritic doses of HEPp did not induce any detectable subacute toxic side-effect in mice whose host defense mechanisms is active as we can observe in mice with CIA.

Suppression of T and B cell responses by Pterodon pubescens seeds ethanolic extract.

The anti-arthritic property of hydro alcoholic extract of Pterodon pubescens seeds was previously demonstrated using the Collagen Induced Arthritis (CIA) in mice, the most similar arthritis experimental model to human rheumatoid arthritis. This disease is characterized by chronic inflamed joints resulting from exacerbated functions of macrophages and T and B lymphocytes. Anti-inflammatory and antinociceptive activities by ethanolic extract of Pterodon pubescens seeds (EEPp) have been also reported. This study describes the effects of EEPp on T and B lymphocytes functions from healthy mice. Delayed Type Hypersensitivity (DTH), in vivo antibody production, T and B lymphocyte proliferation and NO production were determined. Mice treated orally for 7 days with EEPp had inhibited 58% of B cell antibody production (10(-3) mg kg(-1) b.wt.) and 33% of the DTH response (10(-4) mg kg(-1) b.wt.), also reducing tissue leukocyte infiltration. EEPp (10(-2) mg mL(-1)) also inhibited in vitro T (89%) and B (68%) lymphocytes proliferation and NO production (53%) by macrophage cell line J774. The immunosuppression here described for EEPp supports its potential therapeutic use to control exacerbated humoral and/or cellular immune response as in autoimmune and chronic inflammatory diseases.

Eicosanoid-mediated proinflammatory activity of Pseudomonas aeruginosa ExoU.

As Pseudomonas aeruginosa ExoU possesses two functional blocks of homology to calcium-independent (iPLA(2)) and cytosolic phospholipase A(2) (cPLA(2)), we addressed the question whether it would exhibit a proinflammatory activity by enhancing the synthesis of eicosanoids by host organisms. Endothelial cells from the HMEC-1 line infected with the ExoU-producing PA103 strain exhibited a potent release of arachidonic acid (AA) that could be significantly inhibited by methyl arachidonyl fluorophosphonate (MAFP), a specific PLA(2) inhibitor, as well as significant amounts of the cyclooxygenase (COX)-derived prostaglandins PGE(2) and PGI(2). Cells infected with an isogenic mutant defective in ExoU synthesis did not differ from non-infected cells in the AA release and produced prostanoids in significantly lower concentrations. Infection by PA103 induced a marked inflammatory response in two different in vivo experimental models. Inoculation of the parental bacteria into mice footpads led to an early increase in the infected limb volume that could be significantly reduced by inhibitors of both COX and lipoxygenase (ibuprofen and NDGA respectively). In an experimental respiratory infection model, bronchoalveolar lavage (BAL) from mice instilled with 10(4) cfu of PA103 exhibited a marked influx of inflammatory cells and PGE(2) release that could be significantly reduced by indomethacin, a non-selective COX inhibitor. Our results suggest that ExoU may contribute to P. aeruginosa pathogenesis by inducing an eicosanoid-mediated inflammatory response of host organisms.