Eosinophil locomotion and the release of IL-3 and IL-5 by allergen-stimulated mononuclear cells are effectively downregulated in vitro by budesonide.
BACKGROUND
Treatment of allergic asthma with inhaled corticosteroids, such as budesonide (BDN), results in downregulation of T-cell activation and of eosinophil recruitment.


OBJECTIVE
Since blood concentrations of BDN, although significantly lower than those measured in the lung, may still have anti-inflammatory effects, we evaluated the activity of BDN in vitro on: allergen-induced release of lymphokines involved in eosinophil chemotaxis (i.e. IL-3 and IL-5), at drug concentrations similar to those obtained in vivo in the lung (10-8 M), and eosinophil locomotion, at "systemic concentrations' of the drug (10(-10)M and 10(-9)M).


METHODS
Twenty-three atopic asthmatic subjects (atopics) sensitized to Dermatophagoides pteronyssinus (Dp) and seven non-atopic healthy subjects (controls) were studied. Purified blood mononuclear cells (BMC) were stimulated with Dp, with or without BDN 10(-8) M and, after 6 days, the supernatants were collected and frozen to test their chemotactic activity toward purified blood eosinophils and their levels of interleukin (IL)-3 and IL-5 by immunoassay. BMC were then pulsed for additional 18 h with [3H]thymidine to evaluate allergen-induced T-cell proliferation. In addition, to test possible direct effects of 'systemic concentrations' of the drug on eosinophil locomotion, blood eosinophils were incubated for 1 h with BDN (10(-10) M and 10(-9) M) prior to test their chemotactic response toward recombinant human IL-3 and IL-5.


RESULTS
Stimulation of BMC from atopics with Dp induced a statistically significant increase in [3H]thymidine incorporation (P < 0.05); secretion of chemotactic factors for eosinophils (P < 0.001) and the release of IL-3 and IL-5 (P < 0.005 and P < 0.05 respectively). BDN, at the concentration of 10(-8) M, was able to significantly down-regulate T-cell proliferation (P < 0.05), the secretion of chemotactic factors for eosinophils (P < 0.001) and the release of IL-3 and IL-5 (P < 0.01 and P < 0.05 respectively). Similarly, "systemic concentrations' of BDN (10(-10) M and 10(-9) M) totally inhibited the chemotactic response of blood eosinophils toward recombinant human IL-3 and IL-5 (P < 0.005).


CONCLUSIONS
Concentrations of BDN similar to those obtained in vivo are effective in inhibiting both the release of eosinophils chemotaxins by allergen-activated mononuclear cells and eosinophil locomotion.
Lantero
S
S
Divisione di Pneumologia, G. Gaslini Institute, Genoa, Italy.
Sacco
O
O
Scala
C
C
Morelli
M C
MC
Rossi
G A
GA
D000293:Adolescent; D000485:Allergens / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D039741:Antigens, Dermatophagoides; D001249:Asthma / Q000097:blood; D019819:Budesonide; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D002648:Child; D015536:Down-Regulation / Q000187:drug effects; D004804:Eosinophils / Q000166:cytology* / Q000187:drug effects; D005260:Female; D006023:Glycoproteins / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007377:Interleukin-3 / Q000378:metabolism*; D015848:Interleukin-5 / Q000378:metabolism*; D008297:Male; D011282:Pregnenediones / Q000494:pharmacology*
D000485:Allergens; D000893:Anti-Inflammatory Agents; D039741:Antigens, Dermatophagoides; D006023:Glycoproteins; D007377:Interleukin-3; D015848:Interleukin-5; D011282:Pregnenediones; D019819:Budesonide