Anti-inflammatory effects of UV-irradiated lymphocytes: induction of IL-1Ra upon phagocytosis by monocyte/macrophages

Oxidative Stress and Treg and Th17 Dysfunction in Systemic Lupus Erythematosus

“…UV radiation exposure is among the environmental factors that have been studied the most with respect to association with SLE [55, 56]. While experimental studies show a significant immunomodulatory role for UV radiation, epidemiologic data describe its role in triggering SLE onset and patient deterioration [55–59]. To date, we understand that both UVB and UVA play a role in the pathogenesis of lupus erythematosus [58].…”

Apoptosis: A target for potentiation of UV-induced IL-1Ra synthesis by IVIg

“…This in vitro study indicates that through their capacity to induce apoptosis [28,29] and to activate IL-1Ra production [16], IVIg modes of action display striking analogies with those of UV [23,24], a characteristic which might constitute a basis for their marked ability to potentiate UV-induced cytokine production. However, the underlying mechanisms are different with low dose and high dose IVIg.…”

“…By allowing lymphocytes to reach a critical apoptosis level during a defined pre-incubation period [24] followed by their phagocytosis by monocytes/macrophages, the requirement for PBMC preactivation by LPS [23] prior to addition of UV-irradiated lymphocytes in order to produce immunosuppressive cytokines could be avoided. This process constituted by itself a sufficient and preferential stimulus for IL-1Ra production leaving IL-10 unaffected [24]. Likewise, potentiation of UV induced cytokine synthesis by IVIg also preferentially oriented it towards IL-1Ra production rather than IL-10.…”

“…Furthermore, by applying a slightly modified UV-irradiation procedure [23,24], and using IVIg at high and low concentrations, cytokine secretion could be oriented towards preferential IL-1Ra production. By allowing lymphocytes to reach a critical apoptosis level during a defined pre-incubation period [24] followed by their phagocytosis by monocytes/macrophages, the requirement for PBMC preactivation by LPS [23] prior to addition of UV-irradiated lymphocytes in order to produce immunosuppressive cytokines could be avoided.…”

“…More recently, the capacity of UV-irradiation to induce marked activation of IL-1Ra production has been documented on PBMC obtained by apheresis during extracorporeal photochemotherapy [23] and on in vitro UV-irradiated PBMC [24]. A mechanism consisting of lymphocyte apoptosis followed by increased phagocytosis by monocytes-macrophages [25,26] leading to production of immunosuppressive and antiinflammatory cytokines, has been proposed [27].…”