IL-4 is an endogenous inhibitor of neutrophil influx and subsequent pathology in acute antibody-mediated inflammation.
IL-4 is an immunoregulatory cytokine that has in vitro and in vivo anti-inflammatory actions. In this study we investigated whether endogenously produced IL-4 modulates inflammatory processes that occur after Abs bind to target tissue by comparing the severity of glomerulonephritis induced by heterologous anti-glomerular basement membrane Abs in wild-type (IL-4+/+) mice to that of glomerulonephritis induced in homozygous IL-4 gene knockout (IL-4-/-) mice. Two hours after Ab injection, IL-4-/- mice had significantly higher intrarenal intercellular adhesion molecule-1 mRNA expression and intraglomerular neutrophil accumulation than the IL-4+/+ group. Treatment of IL-4-/- mice with recombinant murine IL-4 at the time of disease induction reduced intercellular adhesion molecule-1 expression and neutrophil influx to levels observed in IL-4+/+ kidneys. Four days after Ab administration, untreated IL-4-/- mice developed significantly greater urinary protein excretion, intracapillary fibrinogen deposits, and glomerular hypercellularity than IL-4+/+ mice. These results demonstrate that endogenous IL-4 suppresses neutrophil influx and limits tissue damage in Ab-induced glomerulonephritis, suggesting that IL-4 is an important regulator of acute inflammatory processes.
Saleem
S
S
Renal Division, Emory University School of Medicine, Atlanta, GA 30033, USA.
Dai
Z
Z
Coelho
S N
SN
Konieczny
B T
BT
Assmann
K J
KJ
Baddoura
F K
FK
Lakkis
F G
FG
D000208:Acute Disease; D000818:Animals; D001323:Autoantibodies / Q000502:physiology*; D001485:Basement Membrane / Q000276:immunology / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology*; D005921:Glomerulonephritis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology; D011507:Proteinuria / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D001323:Autoantibodies; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1; D015847:Interleukin-4