Simplified hypothetical model demonstrating the sites of action of anti-arthritic therapeutics used in this study. sPLA2 IIa provides the substrate for the production of the inflammatory mediators; platelet-activating factor (PAF), prostaglandins and leukotrienes. Additionally, sPLA2 IIa is a ligand for the M-type receptor: sPLA2 IIa agonist activity causes mast cell degranulation and activation of neutrophils. Ibuprofen, leflunomide and infliximab all act on inflammatory mediators downstream of sPLA2 IIa actions. Prednisolone globally alters inflammatory gene transcription. AA, arachidonic acid; cPLA2, cytosolic phospholipase A2; PAF, platelet activating factor; MAP kinase, mitogen activated protein kinase; M-type receptor, muscle type receptor; sPLA2 IIa, secretory phospholipase A2 group IIa; TNFα, tumour necrosis factor alpha.
Coulthard et al. Arthritis Research & Therapy 2011 13:R42 doi:10.1186/ar3278