Role of IL-10 in the abnormalities of early cell activation events of lymphocytes from patients with systemic lupus erythematosus

Lymphocytes from patients with systemic lupus erythematosus (SLE) exhibit abnormalities in early cell activation events as well as increased production of IL-10. We explored the possible role of IL-10 on defective cell activation events of SLE lymphocytes and first studied the in vitro effect of IL-10 on peripheral blood mononuclear cells (PBMNC) from healthy subjects. After 5 days of culture in the presence of exogenous IL-10, these cells demonstrated abnormal expression of CD69 as well as high intracellular pH and defective activation of the Na%2b/H%2b anti-porter by PMA. We then investigated the effect of IL-10 blockade on PBMNC from SLE patients. SLE PBMNC cultured for 5 days with a blocking anti-IL-10 monoclonal antibody (mAb) partially corrected abnormalities in CD69 expression and intracellular pH; however, in 1/5 patients studied, no significant positive effect was observed. The effect of the anti-IL-10 mAb was apparently not related to protection against activation-induced cell death. We conclude that IL-10 in normal PBMNC induce some of the defects in early cell activation events seen in SLE lymphocytes. Accordingly, the blockade of IL-10 partially corrects these abnormalities in SLE cells. Our data further support the importance of IL-10 in immune dysfunction seen in SLE.

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