Interleukin-1 Receptor Antagonist Suppresses Contact Hypersensitivity

Kondo, Seiji; Pastore, Saveria; Fujisawa, Hiroshi; Shivji, Gulnar M.; McKenzie, Roderick C.; Dinarello, Charles A.; Sauder, Daniel N.
September 1995
Journal of Investigative Dermatology;Sep95, Vol. 105 Issue 3, p334
Academic Journal
Interleukin-1 receptor antagonist (IL-1ra), a naturally occurring inhibitor of interleukin-1 (IL-1), blocks IL-1 binding to its receptors but has no agonistic activity. IL-1 Is thought to play an important role in contact hypersensitivity (CHS), although the effects of exogenously administered IL-1 in CHS have been somewhat controversial. To clarify the role of IL-1 in CHS, we studied the effect of IL-1 receptor blockade using exogenous a-Ira and evaluated these effects on CHS. We examined the in vivo effects of local administration of recombinant human IL-1ra in the inurine CHS model. Local injection of IL-1ra to sensitized BALB/c mice just before challenge with dinitrofluorobenzene resulted in a significant reduction in the intensity of CHS responses, assessed by ear swelling. A dose-response study revealed that maximal inhibition of ear swelling (36% to 43%) was observed after intradermal injection of IL-1ra at doses of 10 to 100 μg/ear. This reduction in ear swelling in IL-1ra-injected ears consisted of less inflammatory cell infiltration and decreased edema in the dermis compared with controls. Suppression of CHS was observed when IL-1ra was applied in the 24-h interval preceding challenge with dinitrofluorobenzene, whereas no suppressive effect was observed when IL-1ra was applied 48 h before or after the challenge. Local administration of IL-1ra to naive mice 5 h before sensitization also suppressed CHS responses. However, a-1ra injection did not suppress phenol-induced inflammation. These results suggest that IL-1ra is an effective inhibitor of both the sensitization and elicitation phases of CHS expression in mice, thus emphasizing the role of IL-1 as an immunologic potentiator of responses associated with CHS.


Related Articles

  • In Vivo Administration of Interleukin 1 to Normal Mice Depresses Their Capacity to Elicit Contact Hypersensitivity Responses: Prostaglandins Are Involved in This Modification of Immune Function. Robertson, Bekkie; Gahring, Lorise; Newton, Robert; Daynes, Raymond // Journal of Investigative Dermatology;Apr87, Vol. 88 Issue 4, p380 

    The administration of pyrogenic doses of interleukin 1 (IL-1) to normal mice before contact sensitization with dinitrofluorobenzene (DNFB) resulted in a significant reduction in the intensity of the elicited contact hypersensitivity (CH) responses. Adoptive transfer experiments established no...

  • Dermatology.  // Clinical & Investigative Medicine;Aug97 Supplement, Vol. 20, pS14 

    Presents an abstract of the research manuscript `Immunosuppressive role of IL-10 in contact hypersensitivity is mainly mediated by modulating IL-1alpha and IL-1beta production,' by G.M. Shivji, P. Toto et al from the University of Toronto.

  • Granuloma Annulare Presenting as Contact Dermatitis. Marty, Chelsy L.; Cheng, Janet F. // Dermatitis (Decker Publishing);Mar2005, Vol. 16 Issue 1, p34 

    Granuloma annulare is a benign idiopathic disorder of the dermis that has various clinical presentations and an unknown etiology. We discuss a patient who presented with a contact dermatitis that demonstrated granuloma annulare on biopsy. The most likely etiologic agent was a substance known as...

  • Herbal medicines.  // Reactions Weekly;8/29/2009, Issue 1267, p19 

    The article describes the two cases of patients who suffered acute irritant contact dermatitis following the treatment of Plantago major for its analgesic and wound-healing properties and covering the leaves with a cloth. A 36-year-old male patient experienced oedema, erosions, erythema, and...

  • SUPPRESSION OF CONTACT SENSITIZATION IN MAN BY PRIOR FEEDING OF ANTIGEN. Lowney, Edmund D. // Journal of Investigative Dermatology;Aug73, Vol. 61 Issue 2, p90 

    Small amounts of dinitrochlorohenzene (DNCB) in capsule from were fed to 63 adult male volunteers, following which these subjects and 60 control subjects were simultaneously subjected to a sensitizing series of topical applications of the same compound. After sensitization had been achieved, the...

  • Alpha-Melanocyte Stimulating Hormone Modulates Contact Hypersensitivity Responsiveness in C57/BL6 Mice. Rheins, Lawrence A.; Cotleur, Anne L.; Kleier, Ruth S.; Hoppenjans, William B.; Saunder, Daniel N.; Nordlund, James J. // Journal of Investigative Dermatology;Oct89, Vol. 93 Issue 4, p511 

    The neuropeptide alpha-melanocyte stimulating hormone (α-MSH) can act as an antagonist to interleukin 1 (IL-1) bioactivities such as inhibition of fever production, thymocyte proliferation, and inhibition of release of acute phase inflammatory molecules from the liver. In this report we have...

  • Cytokine Gene Expression during the Elicitation Phase of Contact Sensitivity: Regulation By Endogenous IL-4. Asada, Hideo; Linton, Jay; Katz, Stephon I. // Journal of Investigative Dermatology;Apr97, Vol. 108 Issue 4, p406 

    Recent studies have focused on characterizing the cytokine profile produced in the epidermis during the sensitization phase of contact sensitivity (CS). Some prior studies have also identified altered individual cytokine mRNA profiles in skin or draining lymph nodes (or several cytokine mRNA...

  • The Prospect of Treating Rheumatoid Arthritis with Recombinant Human Interleukin-1 Receptor Antagonist. Bresnihan, B. // BioDrugs;2001, Vol. 15 Issue 2, p87 

    The prospect of introducing a potent novel therapy that specifically targets a pivotal mediator of disease offers new hope to patients with rheumatoid arthritis (RA). There is convincing evidence that interleukin-1 (IL-1) plays a critical role in the pathogenesis of RA. In RA, the inadequate...

  • Production of TNF-Alpha by Skin Explants of Dinitrochlorobenzene-challenged Ears in Rats: a Model for the Evaluation of Contact Hypersensitivity. Kataranovski, Milena; Kandolf-Sekulović, Lidija; Milosavljević, Ivica // Vojnosanitetski Pregled: Military Medical & Pharmaceutical Journ;Nov/Dec2002, Vol. 59 Issue 6, p581 

    Background. Contact hypersensitivity (CHS) is a local inflammatory response of the skin following challenge of hapten-sensitized animals. It is the consequence of cell infiltration of derm and the release of inflammation mediators, among which Tumor necrosis factor-alpha (TNF-α) is one of the...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics