The production of pro-inflammatory cytokines, such as interleukin-1 and tumor necrosis factor, is pivotal in the response to infection. However, overproduction of these cytokines might be detrimental. It has been suggested that (n-3) fatty acids suppress inflammation and ameliorate the course of infection by decreasing the production of pro-inflammatory cytokines. We here, review these effects. Use of (n-3) fatty acids induced moderate clinical improvements in rheumatoid arthritis, psoriasis and colitis, but not in systemic lupus erythematosus. Data on critically ill burn or postoperative cancer patients are still inconclusive. The (n-3) fatty acids markedly inhibited sterile inflammation in animal studies and improved survival in some experimental infections. T cell responses decreased in healthy volunteers but remained unchanged or increased in certain patient groups. The production of pro-inflammatory cytokines decreased in most human studies. The (n-3) fatty acids increased cytokine production capacity in mice. Differences in cytokine-producing cell types studied may account for these paradoxical responses in humans and mice. Although the increased cytokine production in mice is partly mediated by effects on prostaglandins, mechanisms of action in other species remain to be elucidated. The (n-3) fatty acids may be of moderate benefit in some chronic inflammatory diseases. Their therapeutic value and possible hazards in critically ill patients remain to be established.

IMPORTANCE Older adults acutely hospitalized are at risk of disability. Trials on comprehensive geriatric assessment (CGA) and transitional care present inconsistent results. OBJECTIVE To test whether an intervention of systematic CGA, followed by the transitional care bridge program, improved activities of daily living (ADLs) compared with systematic CGA alone. DESIGN, SETTING, AND PARTICIPANTS This study was a double-blind, multicenter, randomized clinical trial conducted at 3 hospitals with affiliated home care organizations in the Netherlands between September 1, 2010, and March 1, 2014. In total, 1070 consecutive patients were eligible, 674 (63.0%) of whom enrolled. They were 65 years or older, acutely hospitalized to a medical ward for at least 48 hours with an Identification of Seniors at Risk-Hospitalized Patients score of 2 or higher, and randomized using permuted blocks stratified by study site and Mini-Mental State Examination score (<24 vs Ն24). The dates of the analysis were June 1, 2014, to November 15, 2014. INTERVENTIONS The transitional care bridge program intervention was started during hospitalization by a visit from a community care registered nurse (CCRN) and continued after discharge with home visits at 2 days and at 2, 6, 12, and 24 weeks. The CCRNs applied the CGA care and treatment plan. MAIN OUTCOMES AND MEASURES The main outcome was the Katz Index of ADL at 6 months compared with 2 weeks before admission. Secondary outcomes were mortality, cognitive functioning, time to hospital readmission, and the time to discharge from a nursing home. RESULTS The study cohort comprised 674 participants. Their mean age was 80 years, 42.1% (n = 284) were male, and 39.2% (n = 264) were cognitively impaired at admission. Intent-to-treat analysis found no differences in the mean Katz Index of ADL at 6 months between the intervention arm (mean, 2.0; 95% CI, 1.8-2.2) and the CGA-only arm (mean, 1.9; 95% CI, 1.7-2.2). For secondary outcomes, there were 85 deaths (25.2%) in the intervention arm and 104 deaths (30.9%) in the CGA-only arm, resulting in a lower risk on the time to death within 6 months after hospital admission (hazard ratio, 0.75; 95% CI, 0.56-0.99; P = .045; number needed to treat to prevent 1 death, 16). No other secondary outcome was significant. CONCLUSIONS AND RELEVANCE A systematic CGA, followed by the transitional care bridge program, showed no effect on ADL functioning in acutely hospitalized older patients.

Patients with severe granulocytopenia are more susceptible to severe infections and sepsis. Proinflammatory cytokines such as tumor necrosis factor-α (TNF ), interleukin-1α (IL-1α), and IL-1β play an important role in the pathophysiology of sepsis. The profile of these proinflammatory cytokines after lipopolysccharide (LPS) challenge in cyclophosphamide-induced neutropenic mice was assessed, and possible mechanisms responsible for the modified cytokine production were studied. After LPS, both circulating concentrations of TNF and IL-1α in neutropenic mice were 50% to 200% higher than those of controls, whereas IL-1β concentrations were not modified. The kinetics of cytokine production were similar in neutropenic and control animals. The susceptibility of neutropenic mice to an LPS challenge was increased. The observed overproduction of TNF and IL-1α was not due to a direct effect of cyclophosphamide treatment. Because circulating concentrations of uric acid were increased in the neutropenic mice, the effect of hypouricemic treatment with allopurinol and sodium bicarbonate was investigated; such treatment in neutropenic mice challenged with LPS was followed by an improved survival and a reduced proinflammatory cytokine production towards the concentrations in control mice. Hyperuricemia induced by repeated administrations of uric acid in normal mice led to an increased TNF production after LPS. In conclusion, neutropenic mice respond with enhanced cytokine production and increased susceptibility to an LPS challenge, and hyperuricemia probably plays an important role in this phenomenon.

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