Analysis of interaction of cloned human and/or sheep fetal hemoglobin γ-chain and LPS in augmenting induction of inflammatory cytokine production in vivo and in vitro

We have reported earlier that purified preparations of sheep fetal hemoglobin, but not adult hemoglobin, in concert with non-stimulatory doses of lipopolysaccharide (LPS) (lipid A), act cooperatively to regulate in vitro production of a number of cytokines, including TNFα, TGFβ and IL-6 from murine and human leukocytes. Following in vivo treatment of mice with the same combination of hemoglobin and LPS, harvested spleen or peritoneal cells showed a similar augmented capacity to release these cytokines into culture supernatants. We report below that genetically cloned γ-chain of human or sheep fetal hemoglobin, but not cloned α- or β-chains, can produce this cooperative effect, as indeed can HPLC purified, heme-free, γ-chains derived from cord blood fetal hemoglobin, and that purified haptoglobin completely abolishes the cooperative interaction.