Cytokine‐Mediated Regulation of Granulocyte Colony‐Stimulating Factor Production

Abstract

Granulocyte colony-stimulating factor (G-CSF) is an important regulator of granulopoiesis and an inducer of T helper 2 (Th2)-related cytokines. In this study we investigated the mechanism of cytokine-modulated G-CSF production in lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMC) and bone marrow stromal cells (BMSC). In PBMC, LPS significantly induced G-CSF and interleukin (IL)-1, an inducer of G-CSF. Both were partly inhibited by IL-4, IL-6 and IL-10. None of these effects were the result of altered monocyte activation or proliferation. The effects of IL-4 and IL-10 appeared to be independent of IL-1 suppression or IL-1 receptor antagonist (IL-1ra) induction, but rather seemed to involve a blockade of IL-1 function, in addition to a blockade of IL-1-independent stimulatory effects on G-CSF production. The effect of the IL-6-induced suppression of G-CSF production differed from that of IL-4 and IL-10 in that it was much less pronounced and could be partially overridden by addition of functional IL-1, yet it also appeared to involve the interference with IL-1 function and the suppression of IL-1-independent mechanisms. In BMSC, G-CSF synthesis was regulated differently. Here, IL-1 was the main stimulator of G-CSF release, and the effect of IL-1 was neither affected by IL-10 nor IL-6, while IL-4 had a stimulatory effect. Thus, G-CSF production was found to be differently regulated in distinct cellular compartments, and a cross-regulation between these might be facilitated by IL-4-, IL-6- and IL-10-induced inhibition of IL-1. These results could be important for the understanding of G-CSF production in neutropenic patients during severe infection.

Association of Endogenous G-CSF with Anti-Inflammatory Mediators in Patients with Acute Respiratory Distress Syndrome

“…Thus, G-CSF production was found to be differently regulated in distinct cellular compartments. (36) As mentioned, G-CSF induces in vitro IL-6 production and IL-10 mRNA expression in human neutrophils (19,22) and, possibly, IL-10 production in T cells and monocytes. (29,30) Therefore, the negative correlation of IL-6 and IL-10 with WBC in peripheral blood could reflect the parallel rise of G-CSF in serum, which is known to be inversely correlated with WBC.…”

Natural feline coronavirus infection: Differences in cytokine patterns in association with the outcome of infection

“…Healthy FCoV-infected cats without FIP exhibited the generalised B and T cell hyperplasia already described in a previous study (Kipar et al, 1999(Kipar et al, , 2001a and displayed overall significantly higher IL-10 levels in the spleen as well as significantly lower IL-6, G-CSF and M-CSF levels in the mes lnn when compared to cats with FIP. Reduced IL-6 and CSF transcription could be an effect of IL-10 which is known to downregulate these cytokines in humans (de Waal Malefyt et al, 1991a;Hannen et al, 1999). IL-10 also inhibits release of other cytokines, such as IL-12, TNF and IL-1b (de Waal Malefyt et al, 1991a;Koch et al, 1996).…”

Regulation of steady-state neutrophil homeostasis by macrophages

“…In contrast, IL-1Ra treatment did not rescue neutrophilia in c-FLIP f/f LysM-Cre mice ( Figure 5F). These data suggest that elevated levels of G-CSF are sufficient to drive excess neutrophil production, and that although IL-1R signaling has been shown to induce G-CSF production in some contexts, 26,27 an IL-1-independent pathway for G-CSF production exists in c-FLIP f/f LysM-Cre mice.…”