Interleukin-4 induces proliferation and activation of microglia but suppresses their induction of class II major histocompatibility complex antigen expression.
We recently found that microglia, brain macrophages, express interleukin-4 (IL-4) receptor mRNA in vitro. Since IL-4 exhibits a variety of functions on the cells of monocyte-macrophage lineage, we examined the effects of IL-4 on the functions of microglia. Recombinant IL-4 induced the proliferation of microglia in a dose- and time-dependent manner as determined by MTT colorimetric assay, [3H]thymidine uptake and bromodeoxyuridine (BrdU) incorporation. IL-4 also synergistically enhanced 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. Despite these positive effects on proliferation and activation, IL-4 suppressed 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 immunoregulatory 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 regulatory mechanisms of microglia.
Suzumura
A
A
Department of Neurology, School of Medicine, Fujita Health University, Aichi, Japan.
Sawada
M
M
Itoh
Y
Y
Marunouchi
T
T
D000818:Animals; D001483:Base Sequence; D002455:Cell Division; D016207:Cytokines / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000166:cytology* / Q000378:metabolism*; D008969:Molecular Sequence Data; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D019948:Receptors, Interleukin-4; D011975:Receptors, Mitogen; D015847:Interleukin-4