The prostaglandin E agonist, misoprostol, inhibits airway IL-5 production in atopic asthmatics.
BACKGROUND
Prostaglandin E2 is a potent immunomodulator that inhibits the early and late bronchoconstriction to inhaled allergen, as well as inhibiting the acute allergen-induced release of mediators into the human airway. To determine if the stable prostaglandin E agonist misoprostol could alter the late allergic formation of mediators we measured the appearance of eosinophils and key cytokines in the bronchoalveolar lavage fluid 24 h after allergen instillation.


METHODS
Six atopic asthmatics underwent bronchoscopy, alveolar lavage and antigen instillation followed 24 h later by bronchoalveolar lavage. Eosinophil counts were done, together with measurements of IL-4, IL-5, eotaxin, RANTES and cysteinyl leukotrienes by immunoassay. The study was done in randomized blinded fashion while the volunteers took placebo or 600 microg of misoprostol four times a day (QID).


RESULTS
Misoprostol significantly decreased the appearance of IL-5 late after allergen challenge. Eotaxin levels were reduced, but not statistically significantly. Eosinophil number, RANTES, eosinophil cationic protein and cysteinyl leukotrienes were not altered by misoprostol.


CONCLUSIONS
Misoprostol reduces the formation of IL-5 late after allergen challenge, perhaps by inhibiting eosinophil, mast cell, and/or T lymphocyte production of IL-5. Despite decreases in IL-5 and eotaxin, eosinophils were recruited and activated by allergen.
Sheller
James
J
Center for Lung Research, Vanderbilt University Medical Center, Nashville, TN 37232-2650, USA. james.sheller@mcmail.vanderbilt.edu
Dworski
Ryszard
R
Hagaman
David
D
Oates
John
J
Murray
John
J
D000328:Adult; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D001798:Blood Proteins / Q000032:analysis; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000032:analysis; D047091:Eosinophil Granule Proteins; D004804:Eosinophils; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000188:drug therapy* / Q000503:physiopathology; D015848:Interleukin-5 / Q000096:biosynthesis*; D017998:Leukotriene D4 / Q000032:analysis; D008875:Middle Aged; D016595:Misoprostol / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D012260:Ribonucleases
D001798:Blood Proteins; C515456:CCL11 protein, human; D054413:Chemokine CCL11; D019742:Chemokines, CC; D047091:Eosinophil Granule Proteins; D015848:Interleukin-5; D016595:Misoprostol; D017998:Leukotriene D4; D012260:Ribonucleases