Role of macrophage migration inhibitory factor (MIF) in allergic and endotoxin‐induced airway inflammation in mice

Korsgren, Magnus; Källström, Leif; Uller, Lena; Bjerke, T.; Sundler, F.; Persson, C. G. A.; Korsgren, Olle

doi:10.1080/09629350050024339

Cited by 12 publications

(10 citation statements)

References 36 publications

(15 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In contrast to what was found in a prior report using neutralizing antibodies [51], our results demonstrated that treatment of mice with anti-MIF in the challenge phase markedly diminished the AHR and the eosinophilic inflammation, but not IgE concentration in the serum or inflammatory mediator concentrations in the BALF. One possibility for this discrepancy is an inefficient neutralization of MIF associated to lower frequency or dose of antibody treatment used.…”

Section: Discussioncontrasting

confidence: 99%

“…One could hypothesize that MIF produced by CD4 + cells acts in an autocrine/paracrine fashion regulating the production of IFN-c. On the other hand, the effect of MIF on IL-4 inhibition might involve the action of intracellular MIF. The mechanism by which MIF affects Th cells during the priming phase requires further investigation; however, our results clearly demonstrated that MIF is not required for Th2 polarization.In contrast to what was found in a prior report using neutralizing antibodies [51], our results demonstrated that treatment of mice with anti-MIF in the challenge phase markedly diminished the AHR and the eosinophilic inflammation, but not IgE concentration in the serum or inflammatory mediator concentrations in the BALF. One possibility for this discrepancy is an inefficient neutralization of MIF associated to lower frequency or dose of antibody treatment used.…”

contrasting

confidence: 99%

See 1 more Smart Citation

Macrophage migration inhibitory factor is essential for allergic asthma but not for Th2 differentiation

et al. 2007

View full text Add to dashboard Cite

Macrophage migration inhibitory factor (MIF) is increased in asthmatic patients and plays a critical role in the pathogenesis of asthma. We show here that mice lacking MIF failed to develop airway hyper-responsiveness (AHR), tissue eosinophilia, and mucus metaplasia. Analysis of the bronchoalveolar fluids revealed a substantial reduction of IL-13, eotaxin and cysteinyl-leukotrienes. The lack of these cardinal features of asthma in MIF -/-mice occurs regardless of high concentrations of IL-4 in the lung and OVAspecific IgE in the serum. Antigen-specific lymphocyte proliferation and IL-13 production were similarly increased in the draining lymph nodes of OVA-immunized and challenged MIF -/-mice compared to WT, but were reduced in the spleen of MIF -/-, thus indicating differential roles of MIF in these compartments. Stimulation of naive CD4 + cells with anti-CD3 antibody demonstrated that MIF -/-cells produced increased amounts of IFN-c and IL-4 compared to WT CD4 + cells. Finally, treatment of sensitized BALB/c mice with neutralizing anti-MIF antibody abrogated the development of ARH and airway inflammation without affecting the production of Th2 cytokines or IgE. The present study demonstrates that MIF is required for allergic inflammation, adding important elements to our knowledge of asthma pathogenesis and suggesting that neutralization of MIF might be of therapeutic value in asthma. IntroductionAllergic asthma is a disorder characterized by chronic lung inflammation, reversible airway obstruction and increases in airway hyper-responsiveness (AHR) to nonspecific stimuli. Several studies have provided compelling evidences that the lung infiltrating leukocytes and the proinflammatory mediators they produce initiate cellular damage, amplify the immune response, cause airway physiological changes and tissue remodeling [1]. The airway inflammation of asthma has a predominance of Th2 CD4 + lymphocytes, eosinophils and mast cells infiltrating the lung interstitium. Several studies indicate the existence of a mechanism dependent on IL-5 and eosinophils that induce pulmonary damage and intensify AHR [3][4][5]. In other studies, however, the induction of AHR was observed despite the absence of infiltrating eosinophils, suggesting dissociation between these phenomena [6][7][8][9][10]. Macrophage migration inhibitory factor (MIF) is a pleiotropic molecule and critical mediator of innate and acquired immune responses [11,12]. Pre-formed MIF protein is present in many cell types and is released in response to different stimuli, such as infection and cytokine stimulation [12]. MIF exhibits several proinflammatory functions, including the induction of TNF-a, IL-1 and NO release from macrophages, and the production of arachidonic acid and eicosanoids through the induction of phospholipase A 2 and cyclooxygenase [13,14]. A unique property of MIF is its secretion by immune cells in response to physiological increase in glucocorticoid levels. Once released, MIF can counterregulate the anti-inflammatory effects of steroids on cyt...

show abstract

Section: Discussioncontrasting

confidence: 99%

contrasting

confidence: 99%

Macrophage migration inhibitory factor is essential for allergic asthma but not for Th2 differentiation

et al. 2007

View full text Add to dashboard Cite

show abstract

“…The objective of the experiments described here was to determine the direct effects of two PDE 4 inhibitors, roflumi- LPS challenge, administered as an aerosol or via the intratracheal route, has been shown to induce airway inflammation in mice (Schwartz et al, 1994;Korsgren et al, 2000;Birrell et al, 2004) and rats (Ulich et al, 1995;Haddad et al, 2001). Treatment with roflumilast and piclamilast caused a reduction of neutrophil numbers in the BAL, a finding that agrees with published data.…”

Section: Discussionsupporting

confidence: 75%

“…Cellular inflammation, TNF-␣ levels, and the levels of the neutrophilic chemokines keratinocyte-derived chemokine (KC) and macrophage inhibitory protein (MIP)-2, shown to be established markers of inflammation in response to LPS (Schwartz et al, 1994;Ulich et al, 1995;Korsgren et al, 2000;Haddad et al, 2001;Birrell et al, 2004), were measured in the airway lumen as well as in lung tissue. The effects on these parameters in the circulation were also determined.…”

mentioning

confidence: 99%

Phosphodiesterase Type 4 Inhibitors Cause Proinflammatory Effects in Vivo

McCluskie

Klein²,

Linnevers³

et al. 2006

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Phosphodiesterase type 4 (PDE 4 ) inhibitors are currently being evaluated as potential therapies for inflammatory airway diseases. However, this class of compounds has been shown to cause an arteritis/vasculitis of unknown etiology in rats and cynomolgus monkeys. Studies in rodents have demonstrated the anti-inflammatory effects of PDE 4 inhibitors on lipopolysaccharide (LPS)-induced airway inflammation. The aim of this work was to assess the direct effects of PDE 4 inhibitors on inflammatory cells and cytokine levels in the lung in relation to therapeutic effects. The effects of the PDE 4 inhibitors 3-cyclopropylmethoxy-4-difluoromethoxy-N- [3,5-di-chloropyrid-4-yl

show abstract

“…Only a few reports have examined the potential role of MIF in asthma [12][13][14]. ROSSI et al [12] first reported that MIF levels were increased in BALF from asthmatic patients and that circulating eosinophils could produce MIF upon stimulation in vitro.…”

mentioning

confidence: 99%

Role of macrophage migration inhibitory factor in ovalbumin-induced airway inflammation in rats

Kobayashi

Nasuhara

Kamachi

et al. 2006

European Respiratory Journal

View full text Add to dashboard Cite

Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine that reportedly counteracts the anti-inflammatory effect of endogenous glucocorticoids. There have only been a few reports that demonstrate a potential link between MIF and bronchial asthma. In an attempt to further clarify the precise role of MIF in asthma, the present authors examined the effect of anti-MIF antibody (Ab) on airway inflammation and airway hyperresponsiveness in an ovalbumin-immunised rat asthma model.Actively immunised Brown Norway rats received ovalbumin inhalation with or without treatment of anti-MIF Ab. The levels of MIF in bronchoalveolar lavage fluid were significantly elevated after the ovalbumin challenge.An immunohistochemical study revealed positive immunostaining for MIF in bronchial epithelium, even in nonsensitised rats, and the MIF staining in bronchial epithelium was enhanced after the ovalbumin challenge. Anti-MIF Ab significantly decreased the number of total cells, neutrophils and eosinophils in the bronchoalveolar lavage fluid of the ovalbumin-challenged rats, and also attenuated the ovalbumin-induced airway hyperresponsiveness to ovalbumin and methacholine. However, anti-MIF Ab did not affect the level of serum ovalbumin-specific IgE, suggesting that anti-MIF Ab did not suppress immunisation itself.The results indicate that macrophage migration inhibitory factor plays a crucial role in airway inflammation and airway hyperresponsiveness in asthma.

show abstract

Role of macrophage migration inhibitory factor (MIF) in allergic and endotoxin‐induced airway inflammation in mice

Cited by 12 publications

References 36 publications

Macrophage migration inhibitory factor is essential for allergic asthma but not for Th2 differentiation

Macrophage migration inhibitory factor is essential for allergic asthma but not for Th2 differentiation

Phosphodiesterase Type 4 Inhibitors Cause Proinflammatory Effects in Vivo

Role of macrophage migration inhibitory factor in ovalbumin-induced airway inflammation in rats

Contact Info

Product

Resources

About