Immunomodulatory properties of carbon monoxide (CO). CO can act in different cells to downregulate the immune response. Endothelial cells have increased expression of decay accelerating factor (DAF), diminishing complement activation and vascular injury. These cells also have decreased Toll-like receptors (TLRs) and ICAM-1 expression in CO presence, which reduces leukocyte migration and activation, resulting in less inflammatory cytokines production. CO treatment increases vascular endothelial growth factor (VEGF), hypoxia-inducible factor (HIF)-1a and Bcl-2 expression, which is associated to apoptosis decrease. Neutrophils are also affected by CO, having impaired migration with diminished production of local reactive oxygen species (ROS). Antigen presenting cells (APCs) such as macrophages and dendritic cells (DC) have TLRs expression decreased after CO treatment, impairing their maturation leading to decreased ROS and inflammatory cytokines production, less T cell activation and proliferation and maintained IL-10 production. Although lymphocytes can be influenced by CO through APCs modulation, CO can directly act on lymphocytes by diminishing IL-2 production, which consequently suppresses T cell proliferation. CD4+ T cells are more prompt to develop Treg phenotype, which increases IL-10 production. CD8+ T cells have their alloresponse diminished when treated by CO. The role of CO on B cells, NK and NKT cells activation remains unclear.