Regulatory Role of Th-2 Cytokines, IL-10 and IL-4, in Cardiac Allograft Rejection

• Published in: Experimental and molecular pathology Vol. 69; no. 1; pp. 1 - 9
• Main Authors: Mulligan, Michael S., Warner, Roscoe L., McDuffie, J.Eric, Bolling, Steven F., Sarma, J.Vidya, Ward, Peter A.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.08.2000; Elsevier
• Subjects: AIDS/HIV; Animals; Antibodies, Blocking - immunology; Biological and medical sciences; Graft Rejection - immunology; Graft Rejection - pathology; Heart Transplantation - immunology; Heart Transplantation - pathology; Immunoenzyme Techniques; Interleukin-10 - genetics; Interleukin-10 - pharmacology; Interleukin-10 - physiology; Interleukin-4 - genetics; Interleukin-4 - pharmacology; Interleukin-4 - physiology; Male; Medical sciences; Myocardium - immunology; Myocardium - pathology; Polymerase Chain Reaction; Rats; Rats, Inbred Lew; Recombinant Proteins; RNA, Messenger - metabolism; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Surgery of the heart; Th2 Cells - drug effects; Th2 Cells - immunology; Transplantation, Homologous; Heart; Immunohistochemistry; Graft(material); Rat; Pathogenesis; Cytokine; Rodentia; Transplantation; Homotransplantation; Northern blotting; Rejection; Pathology; Vertebrata; Interleukin 4; Experimental disease; Mammalia; Surgery; Animal; Interleukin 10; T-Lymphocyte; Molecular biology
• ISSN: 0014-4800; 1096-0945
• DOI: 10.1006/exmp.2000.2304

The host response to alloantigen results in T- and B-cell activation, upregulation of Class II MHC antigens, and cytokine production by Th-1 cells, resulting in generation of IL-2 and IFNγ. Th-2 cell responses produce IL-4 and IL-10 which may shift the immune response from the Th-1 pathway to Th-2 responses, favoring Ig production. This could imply that Th-2-related cytokines protect allografts. In the following studies, employing cardiac heterotopic allografts in rats (Brown Norway into Lewis), we investigated regulatory roles of Th-2-related cytokines IL-4 and IL-10. Two strategies were used in animals receiving allografts: antibody-induced blocking of endogenous IL-4 or IL-10 and exogenous administration of either interleukin. Antibody to IL-4 failed to alter the rejection time, whereas anti-IL-10 greatly accelerated the rejection process. Northern blot analysis of RNA from allografted hearts revealed mRNA for both IL-4 and IL-10, while immunostaining showed strong staining for IL-10 and very weak staining for IL-4. Exogenous administration of either IL-4 or 10 caused prolongation of allograft rejection times. These findings suggest that in rat cardiac allografts intrinsic IL-10 functions to attenuate the rejection process.