Effects of baicalin on inflammatory reaction, oxidative stress and PKDl and NF-kB protein expressions in rats with severe acute pancreatitis1.

PURPOSE: To investigate the effects of baicalin on inflammatory reaction, oxidative stress and protein kinase D1 (PKD1) and nuclear factor-kappa B (NF-κB) protein expressions in severe acute pancreatitis (SAP) rats. METHODS: Sixty rats were divided into sham operation, model, and low-, medium- and high-dose baicalin group. SAP model was established in later 4 groups. The later 3 groups were injected with 0.1, 0.2 and 0.4 ml/100 g 5% baicalin injection, respectively. At 12 h, the serum SAP related indexes and inflammatory factors, peripheral blood CD3 and γδT cell percentages, wet/dry ratio and pancreas ascites volume, oxidative stress indexes and PKD1 and NF-κB protein expressions in pancreatic tissue were determined. RESULTS: Compared with model group, in high-dose baicalin group the wet/dry ratio and ascites volume, serum amylase level, phospholipase A2 activity, TNF-α, IL-1 and IL-6 levels, and pancreatic malondialdehyde level and PKD1 and NF-κB protein expression were significantly decreased (P < 0.05), and peripheral blood CD3 and γδT cell percentages and pancreatic superoxide dismutase and glutathione peroxidase levels were significantly increased (P < 0.05). CONCLUSION: Baicalin can resist the inflammatory reaction and oxidative stress, and down-regulate protein kinase D1 and nuclear factor-kappa B protein expressions, thus exerting the protective effects on severe acute pancreatitis in rats.

Effects of baicalin on inflammatory reaction, oxidative stress and PKDl and NF-kB protein expressions in rats with severe acute pancreatitis

Abstract Purpose: To investigate the effects of baicalin on inflammatory reaction, oxidative stress and protein kinase D1 (PKD1) and nuclear factor-kappa B (NF-κB) protein expressions in severe acute pancreatitis (SAP) rats. Methods: Sixty rats were divided into sham operation, model, and low-, medium- and high-dose baicalin group. SAP model was established in later 4 groups. The later 3 groups were injected with 0.1, 0.2 and 0.4 ml/100 g 5% baicalin injection, respectively. At 12 h, the serum SAP related indexes and inflammatory factors, peripheral blood CD3 and γδT cell percentages, wet/dry ratio and pancreas ascites volume, oxidative stress indexes and PKD1 and NF-κB protein expressions in pancreatic tissue were determined. Results: Compared with model group, in high-dose baicalin group the wet/dry ratio and ascites volume, serum amylase level, phospholipase A2 activity, TNF-α, IL-1 and IL-6 levels, and pancreatic malondialdehyde level and PKD1 and NF-κB protein expression were significantly decreased (P < 0.05), and peripheral blood CD3 and γδT cell percentages and pancreatic superoxide dismutase and glutathione peroxidase levels were significantly increased (P < 0.05). Conclusion: Baicalin can resist the inflammatory reaction and oxidative stress, and down-regulate protein kinase D1 and nuclear factor-kappa B protein expressions, thus exerting the protective effects on severe acute pancreatitis in rats.

Expression of Heat Shock Protein 27 in Benign Prostatic Hyperplasia with Chronic Inflammation.

BACKGROUND: Heat shock protein 27 (HSP 27) is known as a mediator in immune response and has been recently found to be expressed in prostate cancer. This study aimed to investigate the role of HSP27 in inflammatory BPH. MATERIAL AND METHODS: Hospitalized BPH patients who received TURP were divided into 4 groups by the presence and degrees of chronic inflammation: non-inflammatory BPH (NI BPH), mild-inflammatory BPH (MI BPH), moderate-inflammatory BPH (MOI BPH), and severe-inflammatory BPH (SI BPH). Expressions of HSP 27, TNF-α, IL-6, and CD3 in prostate tissues and serum of patients were detected by immunohistochemistry and ELISA. RESULTS: Expression of HSP27 in BPH with histological inflammation was significantly higher than in non-inflammatory BPH. In inflammatory BPH groups, HSP27 expression gradually increased along with increasing inflammation. There was a significant correlation between the expression of TNF-α, IL-6, CD3 and HSP27 among different inflammatory BPH groups. CONCLUSIONS: HSP27 expression level is associated with the degree of chronic inflammation in BPH and may participate in the pathological process in inflammatory BPH.

The role of acupoint stimulation as an adjunct therapy for lung cancer: a systematic review and meta-analysis.

BACKGROUND: Lung cancer is the leading cause of death in cancer patients. Clinical studies showed that a variety of acupoint stimulations have been extensively used for lung cancer patients, including needle insertion, injection with herbal extraction, plaster application, and moxibustion. However, the role of acupoint stimulation in lung cancer treatment was not fully reviewed. METHODS: In the present study, we conducted a systematic review and meta-analysis on the role of acupoint stimulation in lung cancer treatment by electronic and manual searching in seven databases, including Ovid (Ovid MEDLINE, AMED, CAB Abstracts, EMBASE), EBSCOhost research databases (Academic Search premier, MEDLINE, CIHAHL Plus), PreQuest (British Nursing Index, ProQuest Medical Library, ProQuest Dissertations & Theses A&I, PsycINFO), and ISI web of knowledge (Web of Science, BIOSIS Citation Index, Biological Abstracts, Chinese Science Citation Database), CNKI, Wanfang Data, and CQVIP. RESULTS: Our study showed that acupoint stimulation has strong immunomodulatory effect for lung cancer patients as demonstrated by the significant increase of IL-2, T cell subtypes (CD3+ and CD4+, but not CD8+ cells), and natural killer cells. Further analysis revealed that acupoint stimulation remarkably alleviates the conventional therapy-induced bone marrow suppression (hemoglobin, platelet, and WBC reduction) in lung cancer patients, as well as decreases nausea and vomiting. The pooled studies also showed that acupoint stimulation can improve Karnofsky performance status, immediate tumor response, quality of life (EORCT-QLQ-C30), and pain control of cancer patients. CONCLUSIONS: Acupoint stimulation is found to be effective in lung cancer treatment, further confirmatory evaluation via large scale randomized trials is warranted.

Influences of weight loss on monocytes and T-cell subpopulations in male judo athletes.

The purpose of this study was to examine weight loss effects on immune function in judo athletes. Six elite male Japanese judo athletes (20.3 ± 0.4 years) were enrolled in this study. They completed usual weight loss programs during 2 weeks preceding an actual competition. Subjects noted the appearance of upper-respiratory tract infection (URTI) symptoms during the study period. Blood samples were obtained at 40 (baseline period: BL) and 3 (weight loss period: WL) days before and 1 day after the competition (AC). The CD3, CD4, CD8, CD56CD3, CD28CD4, CD28CD8, and Toll-like-receptor-4 (TLR-4) CD14 cells were counted by using flow cytometer analysis. The 6 subjects reported 1 headache, 3 runny nose conditions, and 1 coughing instance during the WL. The CD3, CD4, CD8, and CD28CD4 cell counts were significantly lower at WL than at BL (p ≤ 0.05); they reverted to the baseline value at AC. The TLR-4CD14 cells were significantly fewer at WL (p ≤ 0.05); they remained fewer than they had been at BL, even at AC. These results suggest that 2 weeks of weight loss before a competition can impair cell-mediated immune function and induce high susceptibility to URTI in judo athletes. Coaches, support staff, and athletes should monitor athletes' weight loss, hydration status, appearance of URTI symptoms, and immunocompetence such as lymphocytes and monocytes to prevent the physical condition from becoming worse.

Impact of postoperative omega-3 fatty acid-supplemented parenteral nutrition on clinical outcomes and immunomodulations in colorectal cancer patients.

AIM: To investigate the effect of omega-3 fatty acid parenteral supplementation postoperatively on clinical outcomes and immunomodulation in colorectal cancer patients. METHODS: Forty-two patients undergoing radical colorectal cancer resection with an indication for total parenteral nutrition postoperatively were enrolled in this prospective, double-blind, randomized, controlled study. Patients received total parenteral nutrition supplemented with either soybean oil (LCT; Intralipid, Fresenius-Kabi, SO group, n = 21) or a combination of omega-3 fish oil and soybean oil (LCT:fish oil = 5:1, fish oil; Omegaven, Fresenius-Kabi, FO group, n = 21), up to a total of 1.2 g lipid/kg per day for 7 d postoperatively. A same volume calorie and nitrogen was administrated. Routine blood test, biochemistry, systemic levels of IL-6 and TNF-alpha, percentage of CD3+, CD4+, and CD8+ lymphocytes were evaluated preoperatively and on postoperative d 1 and 8. Patient outcome was evaluated considering mortality during the hospital stay, length of postoperative hospital stay, and occurrence of infectious complications. RESULTS: Both lipid regimens were well tolerated. No differences between the two groups were noticed in demographics, baseline blood test, biochemistry, serum levels of IL-6 and TNF-alpha, percentage of CD4+, CD8+ lymphocytes, and ratios of CD4+/CD8+. Compared with those on postoperative d 1, serum IL-6 levels on postoperative d 8 were significantly depressed in the FO group than in the reference group (-44.43 +/- 30.53 vs -8.39 +/- 69.08, P = 0.039). Simultaneously, the ratios of CD4+/CD8+ were significantly increased in the FO group (0.92 +/- 0.62 vs 0.25 +/- 1.22, P = 0.035). In addition, depression of serum TNF-alpha levels (-0.82 +/- 2.71 vs 0.27 +/- 1.67, P = 0.125) and elevation of CD3+ and CD4+ lymphocyte percentage (12.85 +/- 11.61 vs 3.84 +/- 19.62, P = 0.081, 17.80 +/- 10.86 vs 9.66 +/- 17.55, P = 0.084, respectively) were higher in the FO group than in the reference group. Patients in the FO group tended to need a shorter postoperative hospital stay (17.45 +/- 4.80 d vs 19.62 +/- 5.59 d, P = 0.19). No statistically significant difference was found when stratified to mortality and occurrence of infectious complications. CONCLUSION: Postoperative supplementation of omega-3 fatty acids may have a favorable effect on the outcomes in colorectal cancer patients undergoing radical resection by lowering the magnitude of inflammatory responses and modulating the immune response.

Placas hiperqueratósicas palmoplantares / Palmoplantar hyperkeratotic plaques

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[Effect of cellular immune supportive treatment on immunity of esophageal carcinoma patients after modern two-field lymph node dissection].

BACKGROUND & OBJECTIVE: Cellular immunity suppression is marked in patients with esophageal carcinoma, which may be resulted temporarily from surgical injury. This study was to evaluate the effect of cellular immune supportive treatment on cellular immunity of patients with esophageal carcinoma. METHODS: A total of 60 patients with thoracic esophageal carcinoma, received two-field dissection, were randomized into control group and trial (immune supportive treatment) group. The patients in trial group were injected with Shenqi injection after operation; the patients in control group received no immune supportive treatment. Peripheral blood samples were obtained before operation, and 3 and 9 days after operation. AgNOR (argyrophilic nucleolar organizer regions) activity in peripheral blood T lymphocytes was measured by tumor immune microphotometry. T cell subsets were measured by flow cytometry. RESULTS: The proportions of CD3+CD4+ and CD4+/CD8+ cells were significantly higher in trial group than in control group at 3 days after operation (P < 0.05). The amount of AgNOR and proportions of CD3+, CD3+CD4+, CD4+/CD8+, and CD4+CD25+ cells were significantly higher in trial group than in control group at 9 days after operation (P < 0.05). There was no significant difference in 1-year survival rate between the 2 groups (P > 0.05). CONCLUSION: Shenqi injection could obviously improve cellular immunity of the esophageal carcinoma patients after modern two-field dissection.

[Improvement effects of Jincao tablet on immune function of model of hysteromyoma in rats].

OBJECTIVE: To investigate the improvement effects of Jincao tablet on immune function of the model of hysteromyoma in rat and the relationship between the model and pathogenesis. METHOD: Rats were randomly divided into 6 groups: normal group, model group, treatment groups including low,middle and high dosage groups of Jincao tablet and Guizhi Fuling pill. Rats were injected respectively with diethyl stilbestrol and progesterone. The immune apparatus of rats were measured. The levels of CD3, CD4 and CD4/ CD8 in serum were determined by flow cytometer. The estrogen and receptor were measured by radioligand binding assay and pathologic changes of womb tissue were observed microscopically. RESULT: Compared with normal group, the weight of thymus, the levels of CD3, CD4 and CD4/CD8 of model group were significantly decreased, and the levels of estrogen, estrogen receptor and CD8 were obviously increased. Jincao tablet groups were significant difference compared with model group and could alleviate the pathological changes of womb tissue. CONCLUSION: Jincao tablet could improve the levels of immune function of the model of hysteromyoma in rat, and it might play a role in the pathogenesis of leiomyoma.

[Effect of Yishen capsule on serum vascular endothelial growth factor and cell immunity in patients with chronic glomerulonephritis].

OBJECTIVE: To explore the effect of Yishen capsule on the serum vascular endothelial growth factor (VEGF), the cell immunity and the theraphic. METHOD: Serum VEGF and T cell subsets were studied in 30 normal subjects and 83 patients before and after treatment. RESULT: Compare with normal subjects, CD3, CD4, CD4/CD8 were decreased, CD8 and serum VEGF were increased obviously (P <0. 05 or P <0. 01). After three months treatment with YiShen capsule, CD4/CD8 was increased, CD8 and serum VEGF were decreased significantly (P <0.05 or P <0.01). CONCLUSION: Yishen capsule can reduce the proteinuria, increase the function of immunity and improve the clinical symptom of patients with chronic glomerulonephritis, achieved the effects of allevating chronic glomerular sclerosis ultimately.

[Immuno-modulatory effect of somatostatin combined with traditional Chinese medicine on severe acute pancreatitis at early stage: a randomized control trial].

OBJECTIVE: To evaluate the immuno-modulatory effect of short course administration of somatostatin (stilamin) continuously at early stage in patients with severe acute pancreatitis (SAP). METHODS: Thirty-nine patients with SAP (22 men, 17 women; the middle age was 49 years)were randomly allocated into control group (20 patients treated with non-surgical integrated traditional Chinese and Western medicine) and treatment group (19 patients treated with somatostatin administered intravenously at a dosage of 250 mug/h for consecutive 72 hours as well as the treatment for the control group). Laboratory parameters, including the expressions of CD(3), CD(4) and CD(8) in lymphocytes (tested by flow cytometry) and C reactive protein (CRP), and indexes of therapeutic effect, including the occurrence of organic dysfunction, local complication and mortality between the two groups were compared. Another group of 30 healthy volunteers (19 men, 11 women; the middle age was 47 years) were recruited for testing the normal levels of CD(3), CD(4) and CD(8). RESULTS: (1) The levels of CD(3), CD(4) and CD(4)/CD(8) in lymphocytes before treatment in both groups were significantly lower than those in the healthy subjects (P<0.05), but there were no statistical differences between the two groups. At the 4th day, CD(3), CD(4) and CD(4)/CD(8) increased significantly in the treatment group (P<0.05) while no changes in the control group; the levels of CD(4) and CD(4)/CD(8) in the treatment group were also higher than those in the control group (P<0.05). (2) The CRP levels of the 2 groups showed no statistical difference before and 4 days after the treatment, but the CRP level in the treatment group was significantly lower than that in the control group at the 7th day (P<0.05). WBC count, serum levels of amylase, lipase, lactate dehydrogenase, aspartate aminotransferase, as well as the score of APACHE II in the treatment group recovered more quickly than those in the control group (P<0.05). (3) The occurrences of organic dysfunctions, local complications and mortality in both groups were not statistically different. CONCLUSION: The short course administration of somatostatin continuously at early stage can reduce the inflammatory response, up-regulate the cell immune function and improve the conditions of the patients with SAP, but its effect on mortality and morbidity needs further study.

Intracellular production of IL-2, IL-4 and IFN-gamma by peripheral blood CD3+ cells in intermittent allergic rhinitis.

BACKGROUND: Allergic inflammation is mainly driven by type 2 T helper cells. The aim was to assess the changes in production of type 1 and 2 cytokines by CD3+ T cells dependent on natural exposure to allergens in subjects with intermittent allergic rhinitis (IAR) and in non-atopic subjects. MATERIAL: A total of 13 patients with IAR and 13 healthy non-atopics were recruited into the study. 11 patients with IAR were examined during the grass pollen season and 11 patients outside the season, 9 of them were assessed on both occasions. METHODS: A flow cytometric assessment of intracellular expression of IL-2, IL-4 and IFN-gamma by CD3+ cells was performed. For statistical analysis non-parametric tests were used. RESULTS: A tendency to decreased production of IL-4 outside the season was observed (6.94% [3.42-13.33] in season vs. 2.06% [0.7-3.6] out of season). The production of IL-4 was higher in the rhinitic group in the season than in the control group (1.93% [1.07-4.97], p=0.0034) and production of IL-2 was higher both in and outside the season (9.1% [3.94-15.09] and 10.0% [4.79-25.35] vs. 3.64% (2.64-5.03), p=0.037 and 0.045, respectively). IL-4/IL-2 and IL-4/IFN-gamma ratios were higher in the IAR group in the season than outside the season. CONCLUSION: A tendency towards a switch from a predominant type 2 response during natural allergen exposure to its suppression outside the season was found, together with a stable type 1 response.

[Effect of jiawei yupingfeng powder on T-lymphocyte subsets in patients with senile chronic bronchitis in acute onset stage].

OBJECTIVE: To explore the effect of Jiawei Yupingfeng Powder (JYP) on T-lymphocyte subsets in patients with senile chronic bronchitis in acute onset stage (SCB-AOS). METHODS: Patients were divided, according to the randomized controlled principle, into two groups, the 44 patients in the treated group and the 40 in the control group. The conventional western medicinal therapy was given to both groups, but to the treated group, JYP was administered additionally. The therapeutic course to them was 14 days. Changes of CD3, CD4, CD8 and the ratio of them were observed. RESULTS: Increase of CD3, CD4 and CD4/CD8 (P < 0.05) and decrease of CD8 (P < 0.01) were significantly shown in the treated group after treatment, but no change in the control group. Besides, comparison of the total effective rate in the two groups also showed significant difference (P < 0.05). CONCLUSION: Cellular immune function disturbance exists in patients with SCB-AOS, JYP could enhance the efficacy by way of modulating cellular immune function.

Clinical observation in 31 cases of chronic bronchitis at remission stage treated with bufei keli.

To observe the therapeutic effects of a Chinese drug Bufei Keli ([symbol: see text] granules for invigorating the lung) in the treatment of chronic bronchitis at remission stage, 62 cases were randomly divided into a treatment group (treated with Bufei Keli) and a control group (treated with Yupingfeng Keli [symbol: see text]). The results turned out to be that the short-term clinically controlled and markedly effective rate was 77.42% and the long-term relapse-resisting markedly effective rate was 74.2% in the treatment group, which were obviously higher than 45.16% and 38.71% respectively in the control group (P < 0.05). And the increase in contents of SOD and CD3 and the decrease in LPO content in the treatment group were also bigger than that in the control group (P < 0.01). It is therefore concluded that Bufei Keli can improve qi deficiency syndrome and raise the immunity of patients with chronic bronchitis, hence its effect of resisting relapse of chronic bronchitis.

[Immune modulatory and therapeutical effect of shenqi tablet accessory therapy in treating recurrent genital herpes].

OBJECTIVE: To observe the immune modulatory and therapeutical effect of Shenqi tablet (SQT) in treating recurrent genital herpes. METHODS: Sixty-three patients were randomly divided into two groups, the SQT group (34 cases) and the control group (29 cases). The immunologic function of patients was determined before and after treatment and the recurrence rate of two groups was compared. RESULTS: In the SQT group after treatment, CD3, CD4 and CD4/CD8 ratio raised, CD8 percent lowered, serum interleukin 2 (SIL-2) and RBC-C3b raised and serum SIL-2 receptor lowered (all P < 0.05), while in the control group, the above-mentioned parameters were not changed significantly. Follow-up conducted 6 months after treatment showed that the recurrence rate in the SQT group was 26.5% (9 cases), which was lower than that in the control group (72.4%, 21 cases) significantly (P < 0.01). CONCLUSION: SQT has immune modulatory effect in patients with recurrent genital herpes, it could reduce the recurrence rate.

Cognitive-behavioral stress management intervention effects on anxiety, 24-hr urinary norepinephrine output, and T-cytotoxic/suppressor cells over time among symptomatic HIV-infected gay men.

The present study tested the effects of a multimodal cognitive-behavioral stress management (CBSM) intervention on anxious mood, perceived stress, 24-hr urinary catecholamine levels, and changes in T-lymphocyte subpopulations over time in symptomatic HIV+ gay men. Seventy-three men were randomized to either a group-based CBSM intervention (n = 47) or a wait-list control (WLC) condition (n = 26). Men assigned to CBSM showed significantly lower posttreatment levels of self-reported anxiety, anger, total mood disturbance, and perceived stress and less norepinephrine (NE) output as compared with men in the WLC group. At the individual level, anxiety decreases paralleled NE reductions. Significantly greater numbers of T-cytotoxic/suppressor (CD3+CD8+) lymphocytes were found 6 to 12 months later in those assigned to CBSM. Moreover, greater decreases in NE output and a greater frequency of relaxation home practice during the 10-week CBSM intervention period predicted higher CD3+CD8+ cell counts at follow-up.

Allergen-stimulated expression of CD154 (CD40 ligand) on CD3+ lymphocytes in atopic, but not in nonatopic individuals. Modulation by bacterial lipopolysaccharide.

The intention of this study was to mimic a naturally occurring stimulation by allergens and bacterial infection in order to determine whether specific allergen-induced, inflammatory responses may be changed or modified by bacterial products. Blood leukocytes from six atopic and six nonatopic individuals were examined for their surface expression of CD154, CD11a, and HLA-DR molecules and for secretion of IgE, eosinophil cationic protein (ECP), and the cytokines interleukin (IL)-4 and IL-5. Signals through CD154 are required for activation and proliferation of effector cells associated with the allergic, inflammatory response. HLA-DR and CD11a/CD18-mediated interactions are also involved in T- and B-cell functions. Birch-pollen (BP) allergens induced CD154 expression on CD3-positive lymphocytes only in atopic individuals. In nonatopics, the expression of CD154 could be induced only after exposure to BP and subsequent lipopolysaccharide (LPS) stimulation. Levels of CD154 expression were always higher in atopics than nonatopics. CD11a and HLA-DR expressions were upregulated, irrespective of atopic state, after BP and/or LPS stimulation. The increased secretion of IL-5 and total IgE in BP-supplemented cell cultures indicated that an allergic response had occurred. In conclusion, the results of this report do not support the hypothesis of a changed inflammatory response stimulated by the combined action of bacteria and allergens, as compared to allergen provocation alone.

Study on local inflammatory reactions and other parameters during subcutaneous mistletoe application in HIV-positive patients and HIV-negative subjects over a period of 18 weeks.

Subcutaneous injections of fermented and unfermented aqueous extracts of Viscum album L. result in a local inflammatory reaction at the injection site. In this trial, the symptoms associated with this local reaction were investigated. Furthermore the occurrence of local reactions was tried to correlate with an increase in CD3/25- and CD8/38-positive lymphocyte counts, with eosinophilic granulocyte numbers, and with the formation of mistletoe lectin antibodies. Included in the trial were 30 HIV-antibody-positive patients and 17 healthy non-smokers, aged 24-51 years. The CD4 cell count in the HIV-negative subjects was > 800/microliter, compared with 200-600/microliter in the HIV-positive patients. All study participants had a Karnofsky score > or = 70. The trial subjects were observed over a period of 18 weeks. With escalation of the dose of a fermented and unfermented extract of Viscum album L. (Iscador Qu Spezial and Viscum album QuFrF), there was an increase in local reactions. Erythema at the injection site was the most frequently reported symptom. Between the doses and the symptoms induration, swelling and pruritus were marked correlations. Effects of the application of mistletoe extracts on the immune system were demonstrated by an increase in CD3/25-positive lymphocyte counts and antibodies against mistletoe-lectins. There were no changes in eosinophilic granulocytes or CD8/38-positive lymphocyte populations. For evaluation of the therapeutic applications of mistletoe extracts in HIV-positive patients it is advisable to assess primarily activation of CD3-positive lymphocytes and the patient response on the basis of the local reaction. The local inflammatory reaction at the injection site is desirable and well tolerated if the reaction is smaller than 5 cm in diameter.

Advances in immunotherapy of rheumatoid arthritis: clinical and immunological findings following treatment with anti-CD4 antibodies.

Rheumatoid arthritis is a chronic inflammatory disease mainly affecting the joints. The etiology of the disease is still unknown, but it shows several of the clinical and laboratory features of an autoimmune process. Often, efficacy of conventional treatment is not satisfactory in patients with RA and therefore, alternative therapies have to be considered. Since CD4+ T helper cells appear to play an important role in disease pathogenesis, anti-CD4 treatment has been tried in RA patients. This paper will present a summary of our experience including some new recent findings upon immunomodulation caused by anti-CD4. Following anti-CD4 antibody infusion with antibody MAX16H5, a decline in lymphocyte counts has been observed with a depletion of CD3+ T cells to 30%, CD4+ T cells to 13% and monocytes to 33% of pretreatment levels. Moreover, all remaining T helper cells were coated by anti-CD4. No changes in CD8+ T cells or B lymphocytes were noted. After a partial recovery of CD4+ T cells, decreased numbers were maintained for 8 weeks. Modulation of the target antigen was demonstrated by high levels of soluble CD4 and a decreased CD4 antigen density on T helper cells down to 30% of the original level, which reached pretreatment levels 2 weeks after therapy. Proliferative responses to mitogens and antigens were reduced immediately after the antibody infusions but were markedly increased in some patients when compared to the pretreatment situation. In addition, a rapid decrease of monocyte/macrophage activation markers was observed.(ABSTRACT TRUNCATED AT 250 WORDS)