In our study, the two cases showed the loss of cortisol rhythm, elevated cortisol level at 4 pm and decline of cellular immune function in prolonged phase of H7N9 pneumonia. Interestingly, case 2 had higher cortisol level and lower DHEAS levels than case 1, but had lower cellular immune function. One meta-analysis also has demonstrated the association between high cortisol levels and mortality, which made cortisol an useful biomarker for assessing prognosis in patients with severe community-acquired pneumonia (CAP) . Glucocorticoids influence the traffic of circulating leukocytes and inhibit many functions of leukocytes and immune accessory cells . They inhibit cell accumulation at inflammatory sites and reduce the number of circulating lymphocytes, monocytes, and eosinophils by inducing cell apoptosis . Conversely, cytokines, produced by activated immune cells and neuroendocrine cells as well, are able to modulate the hypothalamus-pituitary-adrenal (HPA) axis at each level: the hypothalamus, pituitary, and adrenal glands . DHEAS is a pleiotropic adrenal hormone, primarily regulated by corticotropin, with proimmune and proinflammatory effects, opposing the immunosuppressive effects of glucocorticoids. The high glucocorticoid level and low DHEAS level suggest an imbalance between immunosuppressive and immunostimulatory adrenocortical hormones, which can result in increased susceptibility to infectious complications during the chronic phase of severe illness.
The level of vitamin D in the two patients were all under normal range and case 2 showed hypophosphatemia. Although some studies had shown that vitamin D insufficiency and hypophosphatemia might weaken the host’s immune defense [6, 7], whether or not low level of serum phosphorus and vitamin D would lead to adverse outcome in H7N9 remained unknown. Therefore further studies should be conducted to answer the aforementioned question. One limitation of this study was that we didn’t know whether our patients had low level of 25OH-VitD and serum phosphorus before they had H7N9 pneumonia. But we did need pay more attention to hypophosphatemia and vitamin D insufficiency in severe H7N9 pneumonia. Thus, we used rocalirol to correct vitamin D deficiency in our patient. In our opinion, vitamin D should be measured in severe H7N9 Pneumonia.
The thyroid axis, gonadal and lactotropic axis were normal, so were the level of FT3, FT4, STSH and LH, FSH, T, E2 as well as PRL in these two cases we studied because they were in prolonged but not acute phase of infection.
In conclusion, our cases report suggested that immunoneuroendocrine axis dysfunction might play an important role in severe H7N9 pneumonia. We need pay more attention to hypophosphatemia and vitamin D insufficiency in H7N9 pneumonia.