Inhaled flunisolide suppresses the hypothalamic-pituitary-adrenocortical axis, but has minimal systemic immune effects in healthy cats.
Feline bronchial disease is commonly treated with oral glucocorticoids (OGC), which might be contraindicated in cats with certain infectious, endocrine, renal, or cardiac diseases. Inhalant GC (IGC) maximize local efficacy and minimize systemic bioavailability. We evaluated systemic endocrine and immune effects of IGC (flunisolide, 250 microg/puff q12h) versus OGC (prednisone, 10 mg/d PO) and placebo. Six healthy cats received each drug for 2 weeks followed by a 1-month washout. Testing included determination of single early morning cortisol concentration, results of ACTH stimulation, the urine cortisol-to-creatinine ratio (UC: Cr), lymphocyte phenotype, lymphocyte blastogenesis, serum total IgA and IgM concentrations, and cytokine profiles. Significant differences between treatments were not apparent for serum immunoglobulin concentrations, or expression (mRNA) for the cytokines, interleukin (IL-) 2, IL-4, and IL-10, or gamma interferon. Single early morning cortisol concentration was lower for IGC (0.68 - 0.74 microg/dL), compared with that associated with placebo (2.82 +/- 1.94 microg/dL; P = .033). The ACTH-stimulated peak cortisol concentrations were lower after treatment in cats receiving IGC (before, 8.5 +/- 50.2 microg/dL; after, 2.9 +/- 3.3 microg/dL, P = .0004), but not OGC (before, 8.0 +/- 6.1 microg/dL; after, 6.0 +/- 4.5 microg/dL, P = .07). Similarly, UC: Cr (0.8 +/- 0.8) before IGC was lower than the value (5.02 +/- 3.62; P = .019) after IGC. Compared with placebo, cats given OGC, but not IGC, had significantly lower total percentages of T and B cells. Lymphocyte proliferation was decreased in cats receiving OGC, but not IGC, in comparison with placebo (6.9 +/- 3.3; 24.0 +/- 6.5; 18.8 +/- 14.0, respectively). Significantly more IL-10 mRNA transcription was detected in cats administered OGC or IGC, compared with placebo. Although IGC suppress the hypothalamic-pituitary-adrenocortical axis, IGC had minimal effects on the systemic adaptive immune system.
Department of Pathology, School of Veterinary Medicine, University of California, Davis, CA, USA. reineroc@missouri.edu
Carol R
CR
Reinero
Lisa
L
Brownlee
Kendra C
KC
Decile
Bernard
B
Seguin
Roy D
RD
Berghaus
Richard W
RW
Nelson
Laurel J
LJ
Gershwin
D000280:Administration, Inhalation; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002415:Cats / Q000378:metabolism*; D018592:Cross-Over Studies; D005260:Female; D005446:Fluocinolone Acetonide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D006262:Health; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D007109:Immunity / Q000187:drug effects*; D007070:Immunoglobulin A / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008214:Lymphocytes / Q000145:classification; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism; D011241:Prednisone / Q000494:pharmacology
D018927:Anti-Asthmatic Agents; D007070:Immunoglobulin A; D007075:Immunoglobulin M; D005446:Fluocinolone Acetonide; C007734:flunisolide; D011241:Prednisone; D006854:Hydrocortisone