Induction of interleukin-1beta by interleukin-4 in lipopolysaccharide-treated mixed glial cultures: microglial-dependent effects.
Glial-secreted proinflammatory mediators are dynamically involved in central nervous system responses to exogenous stimuli such as infection, neurotoxins, and nerve injury. The therapeutic use of anti-inflammatory agents may reduce certain central nervous system pathology induced by inflammatory responses. We investigated the role of interleukin (IL)-4 in modulating the production of proinflammatory mediators from lipopolysaccharide-stimulated mixed glia in vitro. Interestingly, IL-4 significantly enhanced IL-1beta secretion and did not affect monocyte chemoattractant protein-1 release, even though IL-4 considerably inhibited IL-6, tumor necrosis factor alpha, and nitric oxide production from rat neonatal mixed glia. Further, IL-4 exhibited inhibitory effects on IL-1beta production in microglial-enriched cultures, while significantly increasing IL-1beta production in microglial-depleted glia. The enhancing effect of IL-4 on IL-1beta production was found to be inversely correlated with the percentage of microglia present in the mixed glial population. In summary, IL-4 did not act as a global anti-inflammatory cytokine and in fact, under certain situations enhanced IL-1beta secretion. We conclude that IL-4 exerts its anti-inflammatory effects in a limited and target-specific manner, which is delicately regulated by the cellular microenvironment. Therefore, precaution should be taken when clinically using IL-4 to treat diseases manifested by overt inflammatory responses.
Cao
Ling
L
Department of Anesthesiology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03756, USA.
Fei
Liang
L
Chang
Tina Ting-Lan
TT
DeLeo
Joyce A
JA
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D018920:Coculture Techniques; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004660:Encephalitis / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D005911:Gliosis / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D018836:Inflammation Mediators; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D008070:Lipopolysaccharides; D017628:Microglia / Q000276:immunology* / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000276:immunology / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D016207:Cytokines; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D015847:Interleukin-4