ABSTRACT
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. CONCLUSION: 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.
Subject(s)
Asthma/immunology , Hypersensitivity, Delayed/immunology , Interleukin-1alpha/metabolism , Alum Compounds/administration & dosage , Animals , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/cytology , Cell Count , Eosinophils/pathology , Female , Hemocyanins/administration & dosage , Hemocyanins/immunology , Immunoglobulin E/metabolism , Interferon-gamma/metabolism , Interleukin-1alpha/immunology , Interleukin-5/analysis , Mice , Mice, Inbred BALB C , Neutrophils/pathology , Ovalbumin/administration & dosage , Ovalbumin/immunology , Th2 Cells/immunologyABSTRACT
Two patients with metastatic malignant melanoma developed immediate type hypersensitivity-like symptoms while being treated with recombinant interleukin-(IL-)2 immunotherapy. Both patients showed positive skin prick tests to IL-2, enhanced basophil degranulation in vitro and responded to anti-histamines, but laboratory investigations suggested an IgE-independent, pseudoallergic mast cell degranulation against IL-2.
Subject(s)
Drug Eruptions/diagnosis , Drug Eruptions/etiology , Interleukin-2/adverse effects , Adult , Female , Humans , Interleukin-2/therapeutic use , Male , Middle AgedABSTRACT
We show that human melanoma cells produce retrovirus-like particles that exhibit reverse transcriptase activity, package sequences homologous to human endogenous retrovirus K (HERV-K), and contain mature forms of the Gag and Env proteins. We also demonstrate expression of the pol gene and of Gag, Env, and Rec proteins in human melanomas and metastases but not in melanocytes or normal lymph nodes. The data suggest that expression of retroviral genes and production of retroviral particles is activated during development of melanoma.
