Simultaneous aberrations in Mphi and T cell function adversely affect trauma patients' clinical outcome: a possible faulty IL-13 feedback loop.
Possible defective trauma patients' Mphi-T-cell feedback interactions between T cell IL-13 production and IL-1beta and IL-18 Mphi secretion were assessed. Mphi produced IL-1 and IL-18 augment T cell IL-13, which in turn limits excessive macrophage activation. Immunodepressed patients' T cells (depressed proliferation to alphaCD3 + alphaCD4) had decreased IL-13 production concomitant to aberrant Mphi activities ( upward arrow mTNFalpha, downward arrow IL-10) and consequent multiple organ failure (MOF). Decreased IL-13 levels in patients' T cell and diminished Mphi supernatant augmentation of healthy controls' T cell IL-13 production appeared concomitantly, suggesting patients' aberrant monokine levels might intensify in vivo T cell dysfunction severity. Patients' Mphi supernatants, which failed to augment controls' T cell IL-13 production, had depressed IL-1beta and lower induction of IL-18 than immunocompetent patients' Mphi, but combined addition of IL-1beta and IL-18 restored these Mphis' IL-13 enhancing activity. These data suggest that immunodepressed patients' aberrant monokine and depressed T cell IL-13 production are independent but synergistic contributors to emergence of MOF.
Laudanski
Krzysztof
K
Department of Surgery, University of Rochester Medical Center, 601 Elmwood Ave.-SURG, Rochester, NY 14642, USA.
De
Asit
A
Pellegrini
Joanmarie
J
Miller-Graziano
Carol
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D018793:Interleukin-13 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000502:physiology*; D053661:Interleukin-13 Receptor alpha1 Subunit; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015846:Monokines / Q000378:metabolism; D009102:Multiple Organ Failure / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018123:Receptors, Interleukin / Q000378:metabolism; D053660:Receptors, Interleukin-13; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014947:Wounds and Injuries / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
C508181:IL13RA1 protein, human; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D015846:Monokines; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13