ROLE OF IL-10 IN THE ABNORMALITIES OF EARLY CELL ACTIVATION EVENTS OFLYMPHOCYTES FROM PATIENTS WITH SYSTEMIC LUPUS-ERYTHEMATOSUS

Lymphocytes from patients with systemic lupus erythematosus (SLE) exhi bit abnormalities in early cell activation events as well as increased production of IL-10. We explored the possible role of IL-10 on defect ive cell activation events of SLE lymphocytes and first studied the in vitro effect of IL-10 on peripheral blood mononuclear cells(PBMNC) fr om healthy subjects. After 5 days of culture in the presence of exogen ous IL-10, these cells demonstrated abnormal expression of CD69 as wel l as high intracellular pH and defective activation of the Na+/H+ anti -porter by PMA. We then investigated the effect of IL-10 blockade on P BMNC 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 stu died, no significant positive effect was observed. The effect of the a nti-IL-10 mAb was apparently not related to protection against activat ion-induced cell death. We conclude that IL-10 in normal PBMNC induce some of the defects in early cell activation events seen in SLE lympho cytes. Accordingly, the blockade of IL-10 partially corrects these abn ormalities in SLE cells. Our data further support the importance of IL -10 in immune dysfunction seen in SLE. (C) 1998 Academic Press