Immunomodulatory effects of cardiotrophin-1 on in vitro cytokine production of monocytes & CD4+ T-lymphocytes.

ABSTRACT

Background & objectives: In congestive heart failure (CHF), increased concentrations of several cytokines including cardiotrophin-1 (CT-1) and immunactivation are found. This study was performed to evaluate whether CT-1 can induce in vitro cytokines in monocytes and CD4+ T-lymphocytes of healthy volunteers. Methods: The study was performed in vitro to see whether CT-1 can modulate monocyte or CD4+ T-lymphocyte interleukin (IL)-1β, -2, -4, -5, -10, interferon γ (IFNγ), and tumour necrosis factor α (TNFα) expression by flow cytometry following stimulation with CT-1 alone or together with lipopolysaccharide (LPS) or phorbol myristate acetate (PMA)/ionomycine (iono). Results: CT-1 increased the number of TNFα and IL-1β positive monocytes. LPS induced IL-10, TNFα, and IL-1β in monocytes but only IL-2 in CD4+ T-lymphocytes, whereas PMA/iono induced all cytokines besides IL-5 in monocytes and IL-1β in CD4+ T-lymphocytes. In LPS activated monocytes, CT-1 induced a concentration-dependent reduction in the number of TNFα positive monocytes. After LPS activation, CT-1 decreased the number of CD4+ lymphocytes positive for IL-2, IL-4, and IL-5. In addition, following PMA/iono stimulation, CT-1 initiated a concentration-dependent decrease of CD4+ T-lymphocytes positive for TNFα, IL-4, IL-5, and IL-10. Interpretation & conclusions: The present data show that in vitro CT-1 can activate monocytes and modulate cytokine production of activated CD4+ T-lymphocytes. We speculate that CT-1 may at least be partly responsible for immunactivation in CHF.