Role of Interleukin-10 in the Intracellular Sequestration of Human Leukocyte Antigen-DR in Monocytes during Septic Shock

Thierry Fumeaux, Jérôme Pugin
2002 American Journal of Respiratory and Critical Care Medicine  
Monocytes from many critically ill patients show a low level of (3, 4) . It has recently been proposed that this antiinflammamajor histocompatibility complex type II (MHC II) expression. This tory response could be immunosuppressive (3). Supporting phenomenon is believed to play a role in these patients' increased this theory is the finding that patients with sepsis have imsusceptibility to secondary infections. In the present study, we show paired delayed-type hypersensitivity, cutaneous
more » ... ty, cutaneous anergy to that the level of monocyte human leukocyte antigen (HLA)-DR excommon antigens (5, 6), and are vulnerable to reactivated pression inversely correlates with the degree of severity of the sepsis cytomegalovirus infection (7) . syndrome. The defect of the monocyte HLA-DR expression resides Immune suppression is accompanied by phenotypic in an intracellular sequestration of the MHC II molecules, a postchanges of circulating leukocytes, such as impaired cytokine translational effect. No significant decrease in the rate of transcripproduction in response to lipopolysaccharides (8), a situation tion of HLA-DR, or its major transcriptional inducer, Class II transreminiscent of "endotoxin tolerance" (9). Circulating monoactivator, was noted. The levels of HLA-DR protein produced by cytes have a low surface major histocompatibility complex monocytes from patients with septic shock were comparable to type II (MHC II) expression in this situation (10-12). Taken those from healthy volunteers. Plasma from patients with septic together, these changes have been referred to as "immune shock induced significant HLA-DR endocytosis resulting in deparalysis" (10). The magnitude of the immune paralysis of creased surface HLA-DR expression of normal donor monocytes. patients with sepsis correlates with an increased susceptibility This effect was partially blocked by anti-interleukin (IL)-10 mono- to secondary infections (13) and possibly with late mortality. clonal antibody, but not by antagonists to transforming growth These changes are also observed in other critically ill patients factor-␤ 1 , prostaglandins, or ␤-adrenergic agonists. Altogether, these data suggest that HLA-DR molecules are re-endocytosed and and may represent a risk factor for nosocomial infections, retained intracellularly in monocytes from patients with septic and thus worsen the prognosis of such patients (14) . shock, and that this phenomenon is partially mediated by IL-10.
doi:10.1164/rccm.200203-217oc pmid:12406851 fatcat:wjuqfdxnvrdmtj2ew5m26px5qm