The anti-allergic drug histaglobin inhibits NF-kappaB nuclear translocation and down-regulates proinflammatory cytokines.

The transcription factor NF-kappaB is the central regulator for the expression of various genes involved in inflammation, infection and immune response including the genes for IL-1beta, TNF-alpha, IL-6 and leukocyte adhesion molecules. Here, we show that the anti-allergic drug histaglobin down-regulates the release of IL-1beta, TNF-alpha, IL-6 and IL-10 in human peripheral blood mononuclear cell cultures. This down-regulatory effect becomes even more pronounced when the cultures are simultaneously activated with the T-lymphocyte mitogen phytohemagglutinin (PHA) or with the B-lymphocyte and macrophage activator lipopeptide (P(3)CSK(4)). We also demonstrate that histaglobin inhibits the nuclear translocation of NF-kappaB in response to TNF-alpha or lipopolysaccharide (LPS) in bone marrow-derived macrophages of Balb/c mice. The inhibitory effect of histaglobin on NF-kappaB activation and cytokine release might be responsible for its anti-allergic effect as demonstrated in clinical studies.