IL-4 expression in human T cells is selectively inhibited by IL-1 alpha and IL-1 beta.
Imbalances in anti-inflammatory and proinflammatory cytokines may be responsible for initiation or progression of diverse pathologic states including autoimmune and infectious diseases. IL-4 production of proinflammatory cytokines and IL-12 promotes differentiation and activation of IFN-gamma-producing T cells, but does a counter-regulatory effect of proinflammatory cytokines on IL-4 production exist? This study evaluates the effect of proinflammatory cytokines (IL-1 alpha, IL-1 beta, IL-6, IL-12, and TNF-alpha) on IL-4 production in primary human T cell cultures. PBMCs from healthy individuals were tested for IL-4 production in response to PHA and various cytokines. IL-4 was measured by proliferation of the IL-4-sensitive T cell line (CT.h4S) or ELISA. IL-1 alpha and IL-1 beta inhibited IL-4 production by 20 to 80% in > 92% of healthy individuals (p = 0.0001, paired t-test). IL-12 had an inhibitory effect on PBMC IL-4 production as previously described, but neither IL-6 nor TNF-alpha inhibited IL-4 production. IL-1 had no effect on PHA-induced PBMC or purified T cell proliferation or IL-2 production. IL-4 production by purified T cells stimulated by PHA or the combination of PMA with calcium ionophore (A23187) was inhibited by IL-1, and reconstitution with peripheral blood-derived adherent macrophages had no effect. IL-12 did not inhibit IL-4 production in stimulated purified T cells. Steady state IL-4 mRNA levels were determined by semiquantitative competitive reverse transcribed PCR (RT-PCR). Marked inhibition of IL-4 mRNA levels were seen at 5 h after exposure to IL-1. This interaction between IL-1 and IL-4 may be an important physiologic regulator of the balance between proinflammatory cytokines from activated macrophages and anti-inflammatory cytokines from T cells.
Sandborg
C I
CI
University of California, Irvine 92717, USA.
Imfeld
K L
KL
Zaldivar
F
F
Wang
Z
Z
Buckingham
B A
BA
Berman
M A
MA
D001483:Base Sequence; D000001:Calcimycin / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D017931:DNA Primers; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008969:Molecular Sequence Data; D010835:Phytohemagglutinins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D017931:DNA Primers; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D000001:Calcimycin; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate