Dual role of interleukin-1alpha in delayed-type hypersensitivity and airway hyperresponsiveness.
BACKGROUND
Using a T helper (Th)1/Th2 disease model, we previously showed that genetically determined Th development depends on dendritic cell-derived interleukin (IL)-1alpha. In Leishmania major infections, Th1 immunity develops if IL-1alpha is present during T cell priming, whereas at later time points, IL-1alpha worsens disease outcome. In the present study, we determined the role of IL-1alpha in other Th2-mediated diseases.


METHODS
BALB/c mice were subjected to delayed-type hypersensitivity (DTH) or ovalbumin (OVA)/alum-induced allergic asthma in the presence or absence of IL-1alpha.


RESULTS
In DTH, mice treated with IL-1alpha during sensitization with keyhole limpet hemocyanin (KLH)/alum developed decreased footpad swelling associated with elevated KLH-specific interferon-gamma levels. In asthma, significantly decreased airway hypersensitivity responses (AHRs) were detected upon treatment with IL-1alpha during T cell priming. In contrast to control mice, IL-1alpha-treated mice showed reduced peribronchial inflammatory infiltrates. The bronchoalveolar lavage (BAL) fluid contained significantly decreased eosinophil numbers (approximately 50%), but 4 times more neutrophils. The BAL fluid of IL-1alpha-treated BALB/c exhibited reduced amounts of IL-5 and OVA-specific IgE serum levels. In contrast, IL-1alpha treatment at later time points after sensitization or during allergen challenge worsened AHR, had no effect on lung inflammation and BAL fluid cell composition. Furthermore, cytokine levels (IL-5, IL-13) and antigen-specific IgE were increased or unaltered under these conditions.


CONCLUSIONS
Similarly to leishmaniasis, IL-1alpha administration during sensitization of Th2-mediated allergic reactions suppresses the course of disease by shifting the immune response towards Th1, whereas later treatments worsen disease outcome. Future studies will elucidate the therapeutic value of IL-1alpha in asthmatic patients.
Caucig
Peri
P
Department of Dermatology, Johannes Gutenberg University, Mainz, Germany.
Teschner
Daniel
D
Dinges
Stephanie
S
Maxeiner
Joachim H
JH
Reuter
Sebastian
S
Finotto
Susetta
S
Taube
Christian
C
von Stebut
Esther
E
D000534:Alum Compounds / Q000008:administration & dosage; D000818:Animals; D001249:Asthma / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D004804:Eosinophils / Q000473:pathology; D005260:Female; D006433:Hemocyanins / Q000008:administration & dosage / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007073:Immunoglobulin E / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D053582:Interleukin-1alpha / Q000276:immunology / Q000378:metabolism*; D015848:Interleukin-5 / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000473:pathology; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000534:Alum Compounds; D053582:Interleukin-1alpha; D015848:Interleukin-5; C041524:aluminum sulfate; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin; D006433:Hemocyanins; C032808:keyhole-limpet hemocyanin