Regulatory role of Th-2 cytokines, IL-10 and IL-4, in cardiac allograft rejection.
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 IFN gamma. 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.
Mulligan
M S
MS
Division of Cardiothoracic Surgery, University of Washington Medical Center, Seattle, Washington, 98195, USA.
Warner
R L
RL
McDuffie
J E
JE
Bolling
S F
SF
Sarma
J V
JV
Ward
P A
PA
D000818:Animals; D019138:Antibodies, Blocking / Q000276:immunology; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D016027:Heart Transplantation / Q000276:immunology / Q000473:pathology; D007124:Immunoenzyme Techniques; D016753:Interleukin-10 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D015847:Interleukin-4 / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D009206:Myocardium / Q000276:immunology / Q000473:pathology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology*; D014184:Transplantation, Homologous
D019138:Antibodies, Blocking; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016753:Interleukin-10; D015847:Interleukin-4