Balanço entre ácidos graxos ômega-3 e 6 na resposta inflamatória em pacientes com câncer e caquexia Omega-3 and 6 fatty acids balance in inflammatory response in patients with cancer and cachexia

O emagrecimento, associado à perda de massa magra, é um fenômeno observado com freqüência em pacientes com câncer. Tal condição predispõe o paciente ao maior risco de infecções, pior resposta aos tratamentos implantados e, como conseqüência, desfavorece o prognóstico de cura. Além disso, a desnutrição também está associada à pior qualidade de vida. Dessa forma, algumas terapias têm sido propostas na tentativa de reverter o catabolismo, por meio da atenuação da resposta inflamatória, observado em grande porcentagem de pacientes com câncer e caquexia. Entre elas, a suplementação com ácidos graxos da família ômega-3 pode representar uma estratégia na redução da formação de citocinas pró-inflamatórias, favorecendo a tolerância metabólica dos substratos energéticos e atenuando o catabolismo protéico, com o intuito de melhorar o prognóstico de cura de pacientes com câncer. Entretanto, os estudos mostram alguns resultados conflitantes da suplementação com ômega-3 na resposta imunológica. Por outro lado, em pacientes com câncer, os ensaios clínicos mostraram atenuar a resposta inflamatória e melhorar o estado nutricional. O objetivo deste artigo é realizar uma revisão criteriosa do assunto.<br>Emaciation and loss of lean body mass is a frequent phenomenon observed in cancer patients. This condition leads to infection risk and a poor response to treatment, thus reducing the chances of cure. Furthermore, malnutrition is also associated with a poor quality of life. Therefore, therapies have been proposed in attempt to revert the catabolism observed in most of these patients by attenuating the inflammatory response. Among them, omega-3 fatty acid supplementation may be a strategy to reduce the production of pro-inflammatory cytokines and improve metabolic substrate tolerance, decreasing protein catabolism in order to ameliorate the prognosis of cure in cancer patients. However, studies demonstrate some conflicting results of ômega-3 supplementation on immune response. On the other hand, clinical trials in cancer patients demonstrate that the inflammatory response decreases and the nutritional status improves. The aim of this paper is to elaborate a strict review of the subject

The modulatory effects of prostaglandin-E on cytokine production by human peripheral blood mononuclear cells are independent of the prostaglandin subtype

The production of inflammatory mediators, relevant to (auto)immune diseases and chronic inflammatory conditions, can be modulated by dietary intake of n-3 and n-6 long chain polyunsaturated fatty acids (PUFAs). It was suggested that these effects are related to the formation of different series of eicosanoids, in particular prostaglandin-E (PGE). In this study we investigated whether prostaglandin subtypes metabolized from arachidonic acid (PGE(2)), dihomo-γ-linolenic acid (PGE(1)) or eicosapentaenoic acid (PGE(3)) have different effects on T-cell proliferation and cytokine production in vitro. Freshly isolated human peripheral blood mononuclear cells (PBMC) were stimulated with concanavalin A (ConA) or lipopolysaccharide (LPS) in the presence or absence of exogenous PGE(1), PGE(2) or PGE(3). We found that tumour necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and to a lesser extent interleukin (IL)-10 production was inhibited by all PGE-subtypes in ConA-stimulated PBMC concomitant with unaffected IL-2 levels. The modulated cytokine production of ConA stimulated cells was independent of T-cell proliferation. PGE(2) and PGE(1) moderately stimulated proliferation, while PGE(3) inhibited the proliferative response to some extent. In LPS-stimulated PBMC, TNF-α production was inhibited by all PGE-subtypes, whereas IL-6 remained unaffected and IL-10 production was increased. Time course experiments on the effects of PGE-subtypes on cytokine production after ConA or LPS stimulation showed these effects to be time dependent, but indifferent of the prostaglandin subtype added. Overall, the modulatory effects of PGE on cytokine production were irrespective of the subtype. This may implicate that the immunomodulatory effects of PUFAs, with respect to cytokine production, are not caused by a shift in the subtype of PGE