The Effects of Various Cytokines on Interleukin-6 and Interferon-α Synthesis in Human Peripheral Blood Mononuclear Cells

Abstract

The effect of various recombinant cytokines on the induction of interleukin-6 (IL-6) synthesis induced in adherent and nonadherent cells of human peripheral blood mononuclear cells (PBMNC) by bacterial lipopolysaccharide (LPS) or concanavalin A (CA) was studied. The results showed that human interferon-(HuIFN)-alpha, -beta, and gamma at a concentration of 100-10,000 IU/ml enhanced the LPS-induced IL-6 production in the adherent cell fraction of PBMNC. However, in nonadherent cells, treatment with HuIFN-alpha or -beta inhibited the CA-stimulated IL-6 production in a dose-dependent manner. Recombinant (r) IL-2 enhanced the IL-6 production of the adherent cells, while rIL-1 alone in the absence of other inducer induced IL-6 production in the nonadherent cell fraction. Other cytokines such as the recombinant tumor necrosis factor-alpha (rTNF-alpha) or rIL-6 itself did not modulate IL-6 production in human PBMNC. TNF and the interleukins studied did not affect the Sendai virus-induced IFN production in the adherent cells. In contrast, the different IFNs exerted a significant priming effect.

Effects of interferon-alpha (IFN-α) administration on leucocytes in healthy humans

“…IFN-a injection resulted in the release of multiple pro-inflammatory factors (like IL-6 and IL-8) and of anti-inflammatory factors (IL-10) and the soluble TNF receptors p55 and p75. In line with our results are the (mainly in vitro) reports from Rosztoczy & Content, who demonstrated that IFN-a enhances lipopolysaccharide (LPS)-induced IL-6 production in the adherent cell fraction of human PBMC [27], and of Tilg et al, who showed that IFN-a induces the circulating TNF receptor p55 in healthy human volunteers [28]. Although Aman et al reported downregulation by IFN-a of IL-8 mRNA expression in patients with chronic myelogenous leukaemia [10], Ohashi et al reported IFN-a augmented IL-8 secretion from latently HIV-1-infected U937 cells [29].…”

Production of Interleukin‐4, Interferon (IFN)‐γ and IFN‐α in Human Immunodeficiency Virus‐1 Infection: An Imbalance of Type 1 and Type 2 Cytokines may Reduce the Synthesis of IFN‐α

“…The effects of IL-2 on SVand HSV-1-induced IFN-a response appeared to be at least partially different in our experiments. IFN-g, and to a lesser extent IL-2, enhanced SV-induced IFN-a response in our studies whereas in those of Rostoczy and Content [22], IFN-g but not IL-2 could increase SV-induced IFN-a production. In their experiments, adherent cells were pretreated overnight with IL-2, whereas we induced PBMCs to produce IFN-a in the presence of IL-2, which may account for the differences in the results.…”

“…It has been shown that it specifically promotes differentiation towards the type-1 immune response [19,20]. In addition, various cytokines enhance or down-regulate the virus-induced production of IFN-a in human blood leucocytes [21][22][23]. Together these data indicate that there may be an interaction between natural and adaptive immune responses.…”

IL-12 induced modulation of tumor derived myeloid cell inflammatory responsiveness.

“…Studies have shown that IFNγ enhances the amount of IL-6 secreted in response to LPS in various types of cells (231,232). Our study shows that IL-12 also increases the amount of IL-6 secreted by 4T1 TIMs in response to LPS in a manner that is independent of IFNγ.…”