Blockade of macrophage migration inhibitory factor (MIF) prevents the antigen-induced response in a murine model of allergic airway inflammation.
OBJECTIVE
The role of macrophage migration inhibitory factor (MIF), a proinflammatory cytokine, was tested using a mouse asthma model.


METHODS
One hundred and four male BALB/c mice were used in this study.


METHODS
Mice were actively sensitized with an intraperitoneal injection of ovalbumin (OVA) and challenged with repeated nebulization of 1 w/v% OVA. Polyclonal anti-MIF antibody was intraperitoneally injected at 10 mg/kg during the antigen challenge period.


METHODS
Bronchoalveolar lavage (BAL) was performed 8 h after the last challenge. Airway hyperresponsiveness to inhaled methacholine was measured 24 h after the last challenge.


RESULTS
Antigen challenge to immunized mice induced increase in inflammatory cells and concentration of Th2 cytokines in BAL fluid (BALF), and caused the development of airway hyperresponsiveness. Anti-MIF antibody significantly decreased the numbers of inflammatory cells including macrophages, eosinophils, lymphocytes and neutrophils in BALF from OVA-challenged mice. Prednisolone decreased the numbers of eosinophils, lymphocytes and neutrophils but not macrophages. Anti-MIF antibody reduced airway hyperresponsiveness. Anti-MIF antibody affected neither the cytokine levels in BALF nor the IgE levels in serum.


CONCLUSIONS
MIF was involved in the antigen-induced inflammatory cell accumulation in the lung and airway hyperresponsiveness without affecting immune responses.
Amano
T
T
Pharmaceutical Research Center, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, 411-8731, Japan.
Nishihira
J
J
Miki
I
I
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D019138:Antibodies, Blocking / Q000009:adverse effects / Q000627:therapeutic use; D001249:Asthma / Q000473:pathology* / Q000517:prevention & control*; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000627:therapeutic use; D007249:Inflammation / Q000473:pathology* / Q000517:prevention & control*; D008070:Lipopolysaccharides; D008263:Macrophage Migration-Inhibitory Factors / Q000037:antagonists & inhibitors* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D010993:Plethysmography, Whole Body; D011239:Prednisolone / Q000627:therapeutic use; D012130:Respiratory Hypersensitivity / Q000473:pathology* / Q000517:prevention & control*; D012772:Shock, Septic / Q000517:prevention & control
D000893:Anti-Inflammatory Agents; D019138:Antibodies, Blocking; D008070:Lipopolysaccharides; D008263:Macrophage Migration-Inhibitory Factors; D007073:Immunoglobulin E; D010047:Ovalbumin; D011239:Prednisolone