Role of macrophage migration inhibitory factor (MIF) in allergic and endotoxin-induced airway inflammation in mice.
Macrophage migration inhibitory factor (MIF) has recently been forwarded as a critical regulator of inflammatory conditions, and it has been hypothesized that MIF may have a role in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD). Hence, we examined effects of MIF immunoneutralization on the development of allergen-induced eosinophilic inflammation as well as on lipopolysaccharide (LPS)-induced neutrophilic inflammation in lungs of mice. Anti-MIF serum validated with respect to MIF neutralizing capacity or normal rabbit serum (NRS) was administered i.p. repeatedly during allergen aerosol exposure of ovalbumin (OVA)-immunized mice in an established model of allergic asthma, or once before instillation of a minimal dose of LPS into the airways of mice, a tentative model of COPD. Anti-MIF treatment did not affect the induced lung tissue eosinophilia or the cellular composition of bronchoalveolar lavage fluid (BALF) in the asthma model. Likewise, anti-MIF treatment did not affect the LPS-induced neutrophilia in lung tissue, BALF, or blood, nor did it reduce BALF levels of tumor necrosis factor-alpha (TNF-alpha) and macrophage inflammatory protein-1alpha (MIP-1alpha). The present data suggest that MIF is not critically important for allergen-induced eosinophilic, and LPS-induced neutrophilic responses in lungs of mice. These findings do not support a role of MIF inhibition in the treatment of inflammatory respiratory diseases.
Korsgren
M
M
Department of Physiological Sciences, Lund University Hospital, Sweden. Magnus.Korsgren@mphy.lu.se
Källström
L
L
Uller
L
L
Bjerke
T
T
Sundler
F
F
Persson
C G
CG
Korsgren
O
O
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004804:Eosinophils / Q000276:immunology; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D008263:Macrophage Migration-Inhibitory Factors / Q000276:immunology* / Q000502:physiology; D008264:Macrophages; D051379:Mice; D008810:Mice, Inbred C57BL; D018448:Models, Immunological; D009504:Neutrophils / Q000276:immunology; D010047:Ovalbumin / Q000276:immunology / Q000494:pharmacology; D011014:Pneumonia / Q000276:immunology*; D011817:Rabbits; D014132:Trachea / Q000276:immunology
D008070:Lipopolysaccharides; D008263:Macrophage Migration-Inhibitory Factors; D010047:Ovalbumin