Interleukin 10 inhibits pro-inflammatory cytokine responses and killing of Burkholderia pseudomallei

Abstract

Melioidosis, caused by Burkholderia pseudomallei, is endemic in northeastern Thailand and Northern Australia. Severe septicemic melioidosis is associated with high levels of pro-inflammatory cytokines and is correlated with poor clinical outcomes. IL-10 is an immunoregulatory cytokine, which in other infections can control the expression of pro-inflammatory cytokines, but its role in melioidosis has not been addressed. Here, whole blood of healthy seropositive individuals (n = 75), living in N. E. Thailand was co-cultured with B. pseudomallei and production of IL-10 and IFN-γ detected and the cellular sources identified. CD3− CD14+ monocytes were the main source of IL-10. Neutralization of IL-10 increased IFN-γ, IL-6 and TNF-α production and improved bacteria killing. IFN-γ production and microbicidal activity were impaired in individuals with diabetes mellitus (DM). In contrast, IL-10 production was unimpaired in individuals with DM, resulting in an IL-10 dominant cytokine balance. Neutralization of IL-10 restored the IFN-γ response of individuals with DM to similar levels observed in healthy individuals and improved killing of B. pseudomallei in vitro. These results demonstrate that monocyte derived IL-10 acts to inhibit potentially protective cell mediated immune responses against B. pseudomallei, but may also moderate the pathological effects of excessive cytokine production during sepsis.

Diabetes alters immune response patterns to acute melioidosis in humans

“…Impaired early inflammatory cytokine production (IL‐1β, IL‐12, IFN‐γ, IL‐6, and TNF‐α) leading to uncontrolled bacterial growth has been previously demonstrated in a polygenic diet‐induced mouse model of T2D infected with BP . Furthermore, the stimulation of whole blood from individuals suffering from T2D with BP also revealed lower IFN‐γ and higher IL‐10 responses, with CD3 − CD14 + monocytes being the main producers of IL‐10 . As a group, the acute DM cohort had very poor glycemic control compared to DM outpatients.…”

Direct Biomarkers of Microbial Translocation Correlate with Immune Activation in Adult Zambians with Environmental Enteropathy and Hepatosplenic Schistosomiasis

“…IL-10 is an immunomodulatory cytokine with potent anti-inflammatory properties and IL-10 treatment in IBDs has shown successful results in many mouse models. 52 , 53 In human, a double-blind, placebo-controlled study was conducted to investigate the efficacy and safety of IL-10 treatment in patients with Crohn’s disease. The overall findings showed only trivial and nonsignificant clinical improvement.…”

Eyeing up the Future of the Pupillary Light Reflex in Neurodiagnostics

“…The first branch of this pathway, the vagus nerve, is activated either directly by cytokines (released from innate immune cells) or indirectly through the chemoreceptive cells located in the vagal paraganglia [ 149 ]. The release of pro-inflammatory cytokines needs to be carefully controlled, as excessive or uncontrolled release (also known as a “cytokine storm”) may contribute to the pathogenesis of infections, including the novel coronaviruses SARS and MERS [ 150 , 151 , 152 ], influenza [ 153 ], and Ebola [ 154 ], as well as potential bacterial biothreat agents such as Burkholderia pseudomallei [ 155 ] and Yersinia pestis [ 156 ].…”