EXPRESSION OF TH-1 TH-2 CYTOKINE MESSENGER-RNA IN PERITONEAL EXUDATIVE POLYMORPHONUCLEAR NEUTROPHILS AND THEIR EFFECTS ON MONONUCLEAR CELL TH-1/TH-2 CYTOKINE PRODUCTION IN MRL-LPR/LPR MICE/

Peritoneal exudative polymorphonuclear neutrophils (PEC-PMN) and monon uclear cells (PEC-MNC) were obtained from normal BALB/c and from autoi mmune MRL-lpr/lpr mice (lpr) with different disease severities. The sp ontaneous and mitogen-stimulated expression of T-helper lymphocyte typ e-1 (Th-1) [represented by interferon-gamma (IFN-gamma) and interleuki n (IL-2)] and T-helper lymphocyte type-2 (Th-2) (represented by IL-4 a nd IL-10) cytokine mRNA in these cells was detected by reverse transcr iption-polymerase chain reaction (RT-PCR). The production of these cyt okines was measured by enzyme-linked immunosorbent assay (ELISA). We f ound that the spontaneous expression of Th-1/Th-2 cytokine mRNA in PEC -PMN from autoimmune mice was progressively increased in parallel with disease severity but was not changed by lipopolysaccharide (LPS) stim ulation. By contrast, spontaneous expression of Th-1/Th-2 cytokine mRN A in PEC-MNC from these mice was progressively decreased in parallel w ith disease severity but retained the responsiveness to phytohaemagglu tinin (PHA) stimulation. To determine the effect of PEC-PMN on Th-1/Th -2 cytokine production by PEC-MNC, autologous PEC-PMN and PEC-MNC were co-cultured at MNC:PMN ratios of 5:0, 4:1, 3:2, 2:3, 1:4 and 0:5 with PHA stimulation for 24 hr. The production of cytokines at each ratio was compared with the expected value, by calculation. We found that PE C-PMN from autoimmune mice progressively suppressed the production of IL-4, IL-10 and IFN-gamma whereas the production of IL-2 was enhanced by autologous MNC in parallel with disease severity. These results sug gest that a reciprocal relationship exists in the expression of Th-1/T h-2 cytokine mRNA between PEC-PMN and PEC-MNC in lpr mice in parallel with disease severity. Autoimmune PEC-PMN can exert significant modula tory effects on Th-1/Th-2 cytokine production by autologous MNC in sti mulation.