Extrarenal cytokines modulate the glomerular response to IgA immune complexes.

Abstract

Clinical episodes of IgA nephropathy coincide recurrently with microbial infections. Cytokines produced during such infections may play a role in the pathogenesis of IgA-associated glomerulonephritis. To test this hypothesis, we examined the influence of passively administered proinflammatory cytokines (IL-1, IFN-gamma and IL-6) on the development of glomerulonephritis in an experimental model of IgA nephropathy. Glomerular IgA immune deposits were induced in mice by administration of IgA anti-phosphorylcholine (PC) with either a PC-containing carbohydrate antigen of Pneumococcal C polysaccharide (PnC) or a protein antigen of PC-conjugated bovine serum albumin (PC-BSA). The effect of IL-1 on the IgA-PC-BSA induced glomerular changes resulted in an increase of mesangial hypercellularity that was associated with mild proteinuria and hematuria. Mice treated with IL-1 and IgA-PnC developed diffuse proliferative glomerulonephritis with proteinuria and hematuria. In contrast, IL-6 treatment with IgA-PC-BSA of IgA-PnC failed to exert any significant renal effect. The combination of IL-6 and IL-1, however, intensified the mesangial hypercellularity of the IgA-PC-BSA, and induced severe proliferative glomerulonephritis with inflammatory monocytes and neutrophils infiltrates in the IgA-PnC treated mice. These glomerular changes were also accompanied by increased proteinuria and hematuria. Similarly, the combination of IFN with IL-1 produced histologic changes and compromised renal function more than IFN or IL-1 exerted independently. These results suggest that extrarenal cytokines influence the renal response to IgA immune deposits. We also conclude that a synergy of multiple cytokines and nephritogenic antigens immobilized in glomerular IgA immune deposits may lead to rapid progression of IgA-associated glomerulonephritis.

• Authors: V Montinaro, K Hevey, L Aventaggiato, K Fadden, A Esparza, A Chen, D S Finbloom, A Rifai
• Journal: Kidney international (Kidney Int) Vol. 42 Issue 2 Pg. 341-53 (Aug 1992) ISSN: 0085-2538 [Print] United States
• PMID: 1405317 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antigen-Antibody Complex
• Cytokines
• Immunoglobulin A

Topics

• Animals
• Antigen-Antibody Complex (metabolism)
• Cytokines (pharmacology, physiology)
• Disease Models, Animal
• Female
• Glomerulonephritis, IGA (etiology, pathology, physiopathology)
• Immunoglobulin A (metabolism)
• Infections (complications)
• Kidney Glomerulus (drug effects, immunology, pathology)
• Leukocytes (pathology)
• Mice
• Mice, Inbred C57BL