Activation of proinflammatory macrophages is associated with the inflammatory state of rheumatoid arthritis. Their polarization and activation are controlled by transcription factors such as NF-κB and the AP-1 transcription factor member c-Fos. Surprisingly, little is known about the role of the AP-1 transcription factor c-Jun in macrophage activation. In this study, we show that mRNA and protein levels of c-Jun are increased in macrophages following pro- or anti-inflammatory stimulations. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment cluster analyses of microarray data using wild-type and c-Jun-deleted macrophages highlight the central function of c-Jun in macrophages, in particular for immune responses, IL production, and hypoxia pathways. Mice deficient for c-Jun in macrophages show an amelioration of inflammation and bone destruction in the serum-induced arthritis model. In vivo and in vitro gene profiling, together with chromatin immunoprecipitation analysis of macrophages, revealed direct activation of the proinflammatory factor cyclooxygenase-2 and indirect inhibition of the anti-inflammatory factor arginase-1 by c-Jun. Thus, c-Jun regulates the activation state of macrophages and promotes arthritis via differentially regulating cyclooxygenase-2 and arginase-1 levels.

The differential diagnosis of food intolerance is broad. Therefore, a structured diagnostic algorithm with input from multiple clinical disciplines should be applied. The treatment consists of eliminating the offending substance from the diet as well as medications and psychosomatic support, when indicated.

Asthma, rhinitis and nasal polyps, as well as chronic gastrointestinal irritation and urticaria following acetylic salicylic acid ingestion may suggest intolerance.

Inhibition of cyclooxygenase (COX) is correctly described as the cause of intolerance to acetylsalicylic acid (ASS) and other non-steroidal antirheumatic drugs (NSAR). Nevertheless, the term "salicylate intolerance" gives a misleading impression of the pathological mechanism. The feature common to the drugs which cause this effect is not the chemical structure, but rather the mechanism of action as COX inhibitor (1). In contrast to ASS, a potent and irreversible inhibitor of COX-1 and COX-2, the non-acetylated salicylates are only very weak and reversible inhibitors of the two COX isoenzymes (2). This is of direct clinical significance, as patients with severe ASS intolerance develop no, or only slight, symptoms after treatment with non-acetylated salicylates, such as disalycilic acid (salsalate), which is commonly used in the USA (3).The author recommends that it is particularly important to avoid COX-1 inhibitors. We concur with this, although it should be explicitly mentioned that the intolerance reaction is triggered by inhibi-tion of COX-1 (3). Studies on patients with ASS/NSAR intolerance have found that highly selective COX-2 inhibitors (coxibs) provide a safe therapeutic option for these patients (1, 3). As a legal precaution, the summaries of product characteristics for the coxibs still include the contraindication "ASS/NSAR intolerance", as for all NS-ARs.