Disease activity and cytokine production in mitogen-stimulated peripheral blood mononuclear cells from patients with rheumatoid arthritis.

OBJECTIVE: To test whether there are differences in the levels and ratios of 6 pro- and 3 anti-inflammatory cytokines produced by mitogen-stimulated peripheral blood mononuclear cells (PBMCs) in rheumatoid arthritis (RA) subjects compared to controls. SUBJECTS AND METHODS: 79 participants (42 seropositive RA patients and 37 healthy controls) were enrolled in this study. The production levels in mitogen-stimulated PBMCs of the 6 proinflammatory cytokines (IFN-gamma, TNF-alpha, TNF-beta, IL-8, IL-17, IL-18) and 3 anti-inflammatory cytokines (IL-4, IL-10, IL-13) were assayed by ELISA using kits obtained from Immunotech SA. The ratios of pro- to anti-inflammatory cytokines were calculated for all participants. RESULTS: There were significantly elevated levels of IL-8 and IL-10, and reduced levels of IFN-gamma, IL-4, and IL-17 in mitogen-stimulated PBMC culture supernatants of RA subjects compared to controls. Of the 18 pro-/anti-inflammatory cytokine ratios, 3 ratios (TNF-alpha/IL13, IL-8/IL-4 and IL-8/IL-13) were significantly higher in RA patients compared to controls; and 6 were higher in controls (IFN-gamma/IL-4; IFN-gamma/IL-10; IFN-gamma/IL-13; TNF-beta/IL10; IL-17/IL-10; IL-18/IL-10). CONCLUSIONS: Activated PBMCs of RA patients, regardless of disease activity, showed higher-level production of IL-8 and IL-10 compared to controls; lower-level production of IFN-gamma, IL-4, and IL-17; and elevated ratios of TNF-alpha/IL-13, IL-8/IL-4 and IL-8/IL-13.

Patient demographics and disease variables correlate with distinct cytokine patterns in mitogen-stimulated peripheral blood mononuclear cells from rheumatoid arthritis patients.

There is paucity of literature on the association of peripheral blood cytokine patterns with patient demographics and disease variables in rheumatoid arthritis (RA). We test the hypothesis that there may be differences in peripheral blood levels of inflammatory cytokines in RA subjects according to various disease variables. In this case, we could identify peripheral blood cytokine markers that correlate with different disease variables. Forty-two seropositive RA patients were characterized according to the age at onset, gender, disease duration, severity, activity and ACR functional class. The production levels in mitogen-stimulated PBMCs of five pro-inflammatory cytokines (IFNgamma, TNFalpha, TNFbeta, IL-8, IL-18) and three anti-inflammatory cytokines (IL-4, IL-10, IL-13) were evaluated in these patients and in healthy controls. Several new findings emerge: (1) higher levels of IL-4 correlate with female gender, milder disease, non-erosive disease, and earlier age at onset; (2) higher levels of IL-10 correlate with the requirement of < or =2 DMARDs; (3) higher levels of IL-18 correlate with non-erosive disease and younger age at onset; (4) higher TNFbeta levels correlate with older present age of patients; and (5) higher IL-8 levels correlate with established/late disease. There are several interesting differences in cytokine patterns with respect to age at onset, current age, disease severity, and the number of DMARDs the patients require.

Lupus patients with pulmonary involvement have a pro-inflammatory cytokines profile.

OBJECTIVES: The literature on cytokine response in systemic lupus erythematosus (SLE) is confusing. It is possible that different disease phenotypes have different cytokine profiles. Our aim was to examine the levels of selected pro-inflammatory and anti-inflammatory cytokines in SLE patients with and without pulmonary involvement. METHODS AND SUBJECTS: Patients with SLE were interviewed and were subjected to the pulmonary function test and high-resolution computed tomography studies. Serum levels of interleukin (IL)-6, IL-8, IL-10, Il-12, interferon (IFN) gamma, and tumor necrosis factor (TNF) alpha were estimated by enzyme-linked immunosorbent assay. RESULTS: Forty-nine of the 61 SLE patients had pulmonary involvement. Median levels of IL-8, IFNgamma, and TNFalpha were significantly higher in the pulmonary group as compared to the non-pulmonary group (p = 0.027, 0.027 and 0.002, respectively). Ratios of pro-inflammatory cytokines to anti-inflammatory cytokines were higher in the pulmonary group as compared to the non-pulmonary group as well as in the pulmonary restrictive subgroup compared to the obstructive subgroup. CONCLUSION: Lupus patients with pulmonary involvement have a stronger pro-inflammatory cytokine bias than those without pulmonary involvement.

Th1/Th2 cytokine patterns and clinical profiles during and after pregnancy in women with multiple sclerosis.

Pregnancy in multiple sclerosis (MS) patients is associated with a lower risk of progression and lower rate of exacerbation. These beneficial effects are reversed postpartum. Considering that the pathogenesis of MS appears to involve cell-mediated immune reactivity, and that pregnancy is accompanied by a depressed cell-mediated immunity, it has been proposed that the lower relapse rate and risk of progression of MS during pregnancy may be due to a pregnancy-associated down-regulation of cell-mediated immunity. In addition, pregnancy results in a shift towards a T helper (Th) 2 cytokine profile, which is presumably protective for MS. This study was aimed at investigating the relationship between clinical status of MS and cytokine levels in eight patients with MS who were followed through pregnancy and after delivery. Peripheral blood lymphocytes from these women were stimulated with a mitogen at different time points during and after gestation and the levels of Th1 cytokines (IFNgamma, TNFalpha) and Th2 cytokines (IL-4, IL-10) were estimated by ELISA. It was established that six of the eight MS patients studied showed a distinct shift from a Th2 cytokine bias during pregnancy towards a Th1 cytokine bias after delivery. These results suggest a possible association between decreased incidence of exacerbation of MS in pregnancy and a pregnancy-induced shift towards Th2 cytokine bias.