ANXA1 down regulates IL-1b

Cutaneous leishmaniasis (CL) is characterized by severe local inflammation, predominantly mediated by IL-1β, TNF, and cytotoxicity, mediators associated with tissue damage and lesion development. Given the high rate of therapeutic failure in <i>Leishmania braziliensis</i> infection, the investigation of molecules that regulate inflammatory response, is an adjuvant therapeutical strategy. Here we investigated the effects of Annexin A1 (ANXA1) on the inflammatory response of CL patients. <i>I</i><i>n silico</i> analyses from our previous transcriptome databases showed increased expression of <i>ANXA1</i>, <i>IL1B</i>, and <i>IL10</i> genes in skin biopsies from CL patients when compared to healthy skin from healthy subjects (HS). Also, increased levels of <i>ANXA1</i>, <i>IL1B</i>, and <i>IL10</i> proteins were observed in serum and cultures of skin biopsies in CL patients when compared to HS. The treatment of lesion biopsies with recombinant ANXA1 reduced IL-1β levels without affecting IL-10, indicating a selective anti-inflammatory effect. Additionally, monocyte-derived macrophages from HS produced high levels of ANXA1, IL-1β, and IL-10 upon <i>Leishmania</i> infection. Blockade of FPR2 receptor increased ANXA1 levels. Finally, addition of recombinant ANXA1 to macrophages did not affects the ability of these cells to kill <i>Leishmania</i>. Our findings demonstrate that ANXA1 negatively regulates IL-1β in CL, without impairing anti-inflammatory mechanisms or macrophage microbicidal activity.