IL-6 is an antiinflammatory cytokine required for controlling local or systemic acute inflammatory responses.

Abstract

IL-6 is induced often together with the proinflammatory cytokines TNFalpha and IL-1 in many alarm conditions, and circulating IL-6 plays an important role in the induction of acute phase reactions. However, whether this endogenous IL-6 plays any additional pro- or antiinflammatory roles in local or systemic responses remains unclear. In this study, the role of IL-6 in acute inflammatory responses was investigated in animal models of endotoxic lung or endotoxemia by using IL-6+/+ and IL-6-/- mice. Aerosol exposure of endotoxin induced increased IL-6 and proinflammatory cytokines TNFalpha and MIP-2 and a neutrophilic response in the lung of IL-6+/+ mice. However, the levels of TNFalpha and MIP-2 and neutrophilia were significantly higher in the lung of IL-6-/- mice. The rate of neutrophil apoptosis in these mice was similar to that in IL-6+/+ mice. A low constitutive level of antiinflammatory cytokine IL-10 was not enhanced by endotoxin and remained similar in the lung in both IL-6+/+ and IL-6-/- mice. Systemically, intraperitoneal delivery of endotoxin resulted in much more pronounced circulating levels of TNFalpha, MIP-2, GM-CSF, and IFNgamma in IL-6-/- mice than in IL-6+/+ mice, and administration of recombinant IL-6 to IL-6-/- mice abolished these differences. In contrast, circulating IL-10 levels were induced to a similar degree in both IL-6+/+ and IL-6-/- mice. Thus, our studies reveal that endogenous IL-6 plays a crucial antiinflammatory role in both local and systemic acute inflammatory responses by controlling the level of proinflammatory, but not antiinflammatory, cytokines, and that these antiinflammatory activities by IL-6 cannot be compensated for by IL-10 or other IL-6 family members.

T‐cell‐specific deletion of gp130 renders the highly susceptible IL‐10‐deficient mouse resistant to intestinal nematode infection

“…The level of inflammation was significantly reduced in IL-10 À/À gp130 fl/fl CD4-Cre 1 mice, demonstrating that the disruption of gp130 signalling in T cells leads to a strong decrease in the production of pro-inflammatory Th1 and Th17 cytokines and an abrogation in the recruitment of inflammatory cells. In this context, IL-6, through trans-signalling using sIL-6R, was shown to control the recruitment of neutrophils after acute inflammation [33][34][35]. Taken together, our data implicate a role of gp130 signalling in T cells for sustaining inflammation and perpetuating its chronicity.…”

“…In this context, IL-6, through trans-signalling using sIL-6R, was shown to control the recruitment of neutrophils after acute inflammation [33][34][35]. Taken together, our data implicate a role of gp130 signalling in T cells for sustaining inflammation and perpetuating its chronicity.…”

The rat antigen-presenting lectin-like receptor complex influences innate immunity and development of infectious diseases

“…First, cytokine mRNA levels following 6 h culture were measured by real-time PCR, targets were the classical proinflammatory cytokines tumor necrosis factor-a and IL-1b, the typically anti-inflammatory cytokines IL-10 and transforming growth factor-b, and the pleiotropic cytokine IL-6. [17][18][19][20] In addition, we targeted p19, a subunit for IL-23 related to Th17 response, and two gene products related to the Th1 response, that is IFNg and p35, a subunit for IL-12. However, data for these latter targets are not included as there were no expression differences between DA and R17 rats (p19 and p35) or because the target was almost undetectable (IFNg).…”

Genetic control of susceptibility to infection with Mycobacterium tuberculosis in mice

“…49 IL-6 also behaves as an anti-inflammatory cytokine to control local and systemic inflammatory responses. 54 Additional experiments are required to formally test the candidacy of any of these genes as Trl-1 and Trl-2. Finally, Trl-3 (peak position 18 cM) which accounts for 20% of the phenotypic variance does not show any obvious candidate genes and proteins possibly associated with host inflammatory or immune responses.…”