High levels of interleukin 10 in serum are associated with fatality in meningococcal disease

Abstract

Interleukin 10 (IL-10) suppresses the production of proinflammatory cytokines in vitro and in murine models of endotoxemia and has been suggested as a candidate for treatment of bacterial septicemia. To investigate the role of IL-10 in meningococcal disease, a sandwich IL-10 enzyme-amplified sensitivity immunoassay was used to quantitate IL-10 in serum and cerebrospinal fluid samples from 41 patients with meningococcal bacteremia or meningitis with or without septic shock. High levels of IL-10 were demonstrated in sera from patients with meningococcal septic shock (mean, 21,221 pg/ml; range, 25 to 64,500 pg/ml). All cases involving fatalities had IL-10 levels in serum of Ն1,000 pg/ml (mean, 23,058 pg/ml; range, 1,000 to 64,500 pg/ml). Patients with meningococcal meningitis without septic shock had comparably low concentrations of IL-10 in serum (mean, 119 pg/ml; range, 0 to 1,050 pg/ml) but exhibited compartmentalized release of IL-10 in cerebrospinal fluid. Concentrations of IL-10 in serum were positively correlated with the previously reported concentrations of tumor necrosis factor alpha, IL-6, and IL-8 in serum in the same patients. We conclude that IL-10 is extensively activated along with the proinflammatory cytokines during the initial phase of meningococcal septic shock and that IL-10 is associated with fatality in meningococcal disease.

A modified ex vivo human whole blood model of infection for studying the pathogenesis of Neisseria meningitidis during septicemia

“…The most convincing parallels to clinical observations were found for IL-10. In our experiments this cytokine showed highest increase in those blood samples in which proliferation of B meningococci was detected, thus re£ecting the in vivo situation as reported in SMD patients [5]. The cytokine release observed in the whole blood samples after arti¢cial infection with menin- Fig.…”

“…A 1000-fold increase of IL-6 was reported for a patient who died by lethal septic shock induced by meningococci [7]. Lehmann and colleagues reported from Norway that in patients su¡ering SMD high IL-10 quantities s 1000 pg ml 31 were positively correlated with fatality [5].…”

“…However, in the rare case of disease the clinical outcome can range from meningitis to severe meningococcal disease (SMD), also known as Waterhouse^Friderichsen syndrome. Cytokines which were found in high levels in serum samples of SMD patients are tumor necrosis factor (TNFK) [3], interleukin (IL)-6, IL-8 [4] and IL-10 [5]. High levels of TNFK were found to be associated with circulatory collapse followed by death [3].…”

Thrombin-mediated IL-10 up-regulation involves protease-activated receptor (PAR)-1 expression in human mononuclear leukocytes

“…This could be beneficial in a physiologic inflammatory process, such as wound healing, but could be detrimental in the systemic inflammatory response associated with sepsis. Indeed, high levels of IL-10 have been associated with a poor outcome during human endotoxemia [6]. This could explain why treatment with the IL-10 inhibitor AS101 significantly increases survival of septic mice after cecal ligation and puncture [39].…”

“…Interleukin-10 (IL-10) is a pleiotropic cytokine produced by monocytes/macrophages and also by T helper cell type 0 (Th0) and Th2 lymphocytes [5]. IL-10 possesses anti-inflammatory and immunosuppressive properties, and it circulates in the blood of patients with severe infections [6]. Besides the fact that endogenously produced and exogenously administered IL-10 can reduce the magnitude of the inflammatory response and improve the outcome in models of endotoxemic and bacteremic shock in rodents and primates, increased concentrations of IL-10 have been associated with an adverse clinical outcome.…”