Clinical and immunological effects of low-dose IFN-alpha treatment in patients with corticosteroid-resistant asthma.
BACKGROUND
Interferon (IFN)-alpha is a cytokine that possesses potent anti-viral and immunoregulatory activities. We aimed to assess clinical and immunological effects of low-dose IFN-alpha in patients with severe corticosteroid-resistant asthma with and without Churg-Strauss syndrome. There is currently no efficient pharmacological treatment available for this group of patients.


METHODS
We studied 10 patients with corticosteroid-resistant asthma, in which 3x10(6) IU/day IFN-alpha were administrated in addition to the prednisone dose given already before introduction of the cytokine therapy. The prednisone dose was gradually reduced dependent on the clinical situation and used as a clinical readout to evaluate the efficacy of the cytokine therapy. To distinguish between IFN-alpha- and prednisone-mediated immunological changes, the corticosteroid dose was kept constant for at least 2 weeks upon introduction of the cytokine therapy in seven patients. The effects of treatment on clinical and immunological parameters were measured at 2-4 weeks and 5-10 months depending on the availability of the patient.


RESULTS
Interferon-alpha treatment rapidly improved the clinical situation as assessed by lung function parameters and required prednisone dose. Important immunological changes included: decreased leukocyte numbers, increased relative numbers of CD4+ T cells, increased differentiation of T helper (Th)1 cells, and increased expression of interleukin (IL)-10 in peripheral blood mononuclear cells.


CONCLUSIONS
Interferon-alpha treatment was associated with dramatic improvements in the condition of patients with corticosteroid-resistant asthma with and without Churg-Strauss syndrome. Potential mechanisms of action include the establishment of a correct Th1/Th2 balance and the induction of the anti-inflammatory IL-10 gene.
Simon
H-U
HU
Department of Pharmacology, University of Bern, Bern High-Altitude Clinic Davos-Wolfgang, Davos, Switzerland.
Seelbach
H
H
Ehmann
R
R
Schmitz
M
M
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D015267:Churg-Strauss Syndrome / Q000188:drug therapy / Q000276:immunology; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology / Q000627:therapeutic use*; D016898:Interferon-alpha / Q000276:immunology / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D007155:Immunologic Factors; D016898:Interferon-alpha; D016753:Interleukin-10