Interleukin-1 and histamine are essential for inducing nickel allergy in mice

Background: We previously reported that (a) lipopolysaccharide (LPS) is a potent adjuvant for inducing Nickel (Ni) allergy in mice at both the sensitization and elicitation steps, (b) LPS induces Interleukin-1 (IL-1) and histidine decarboxylase (HDC, the histamine-forming enzyme), and IL-1 induces HDC, (c) Ni allergy is induced in mast cell–deficient, but not IL-1–deficient (IL-1-KO) or HDC-KO mice. Objective: To examine the roles of IL-1 and HDC (or histamine) and their interrelationship during the establishment of Ni allergy. Methods: Ni (NiCl₂) 1 mmol/L containing IL-1β and/or histamine was injected intraperitoneally (sensitization step). Ten days later, test substance(s) were intradermally injected into ear pinnas (elicitation step), and ear swelling was measured. Results: In wild-type mice, Ni + LPS or Ni + IL-1β injection at sensitization step followed by Ni alone at elicitation step induced Ni allergy. In IL-1-KO, injection of Ni + IL-1β (but not Ni + histamine) was required at both sensitization and elicitation steps to induce Ni allergy. In HDC-KO, Ni + IL-1β + histamine at sensitization step followed by Ni + histamine at elicitation step induced Ni allergy. In histamine H1 receptor–deficient mice, IL-1β induced HDC, but was ineffective as an adjuvant for inducing Ni allergy. In wild-type mice, injection into ear pinnas of Ni 10 mmol/L alone or Ni 1 mmol/L + LPS induced IL-1β, HDC and a prolonged swelling of ear pinnas. In non-sensitized mice, injection of IL-1β by itself into ear pinnas in IL-1-KO mice induced prolonged ear swelling. Ni augmented IL-1 production (both IL-1α and IL-1β) and HDC induction in wild-type mice sensitized to Ni. Conclusions: In mice: (a) for inducing Ni allergy, IL-1 is essential at both the sensitization and elicitation steps, and HDC induction is involved in the effect of IL-1, (b) stimulation of H1 receptor is also essential for inducing Ni allergy at both sensitization and elicitation steps, and (c) the ‘sensitization to Ni’ state may be a state where tissues are primed for augmented production of IL-1α and/or IL-1β in response to Ni. (within 300 words, now 300).