INTERLEUKIN-4 INDUCES PROLIFERATION AND ACTIVATION OF MICROGLIA BUT SUPPRESSES THEIR INDUCTION OF CLASS-II MAJOR HISTOCOMPATIBILITY COMPLEXANTIGEN EXPRESSION

We recently found that microglia, brain macrophages, express interleuk in-4 (IL-4) receptor mRNA in vitro. Since IL-4 exhibits a variety of f unctions on the cells of monocyte-macrophage lineage, we examined the effects of IL-4 on the functions of microglia. Recombinant IL-4 induce d the proliferation of microglia in a dose- and time-dependent manner as determined by MTT colorimetric assay, [H-3]thymidine uptake and bro modeoxyuridine (BrdU) incorporation. IL-4 also synergistically enhance d the proliferation of microglia with such colony-stimulating factors as IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF). It also increased acid phosphatase activity and superoxide anion formation by these cells. De spite these positive effects on proliferation and activation, IL-4 sup pressed the IFN gamma-induced class II MHC antigen expression in these cells. Since these effects of recombinant IL-4 were inhibited by the addition of monoclonal antibody against IL-4 receptors, the effects of IL-4 on microglia appear to be a specific function via IL-4 receptors . Although microglia and astrocytes produce a variety of immunoregulat ory cytokines, neither cell produced IL-4 as determined by bioassay or detection of IL-4 mRNA by RT-PCR method. Thus, the exogenous IL-4 may contribute to the accumulation of microglia in or around inflammatory lesions in the central nervous system, and may be involved in the reg ulatory mechanisms of microglia.