Administration of interleukin-12 exerts a therapeutic instead of a long-term preventive effect on mite Der p I allergen-induced animal model of airway inflammation.
Interleukin-12 (IL-12) is a key cytokine, which promotes T helper type 1 (Th1) cell-mediated immunity and inhibits Th2-type responses. It has been previously shown that IL-12 administration during active immunization following a single allergen exposure can prevent antigen-induced increases in immunoglobulin E (IgE) formation, Th2 cytokine production and bronchoalveolar lavage (BAL) eosinophils in a murine model of allergic airway inflammation. Thus, these studies have now been extended and two IL-12 treatment protocols on this murine model were evaluated. Administration of IL-12 during the active immunization strikingly increased Der p I-specific serum IgG2a and transiently decreased the levels of IgG1 and IgE antibodies following multiple allergen challenges. Such early treatment of IL-12 down-regulated IL-5 production and modestly up-regulated interferon-gamma production but did not effect BAL eosinophilia. These results suggest that repeated exposure to antigen and IL-12 is necessary to maintain a persistent Th1-recall response. Furthermore, administration of IL-12 to actively immunized mice, in which Th2-associated responses were established, had a significant effect on IgG2a synthesis and a modest effect on IgE levels, also down-regulation of IL-5 production, and markedly increased interferon-gamma production and abolished recruitment of eosinophils. Therefore, these data indicate that IL-12 can inhibit antigen-induced eosinophil infiltration into airways, despite the existence of a Th2-associated response. Taken together, these studies suggest that IL-12 may be useful as an immunotherapeutic agent in the treatment of such pulmonary allergic disorders as bronchial asthma.
Lee
Y
Y
Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Fu
C
C
Chiang
B
B
D000485:Allergens / Q000276:immunology*; D000818:Animals; D039741:Antigens, Dermatophagoides; D002455:Cell Division / Q000276:immunology; D005260:Female; D006023:Glycoproteins / Q000276:immunology*; D007114:Immunization; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D018664:Interleukin-12 / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D008925:Mites / Q000276:immunology*; D011994:Recombinant Proteins / Q000627:therapeutic use; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology
D000485:Allergens; D039741:Antigens, Dermatophagoides; D006023:Glycoproteins; D007074:Immunoglobulin G; D011994:Recombinant Proteins; D018664:Interleukin-12; D007073:Immunoglobulin E