Our study showed higher IgA levels (i), CD3+/CD4+ T helper lymphocytes and CD3+/CD8+ T suppressor lymphocytes (ii) in the GLN group vs the control group; IL-2 and IL-4 increased, but not significantly in the GLN group vs the control group (iii).
Our study is the first to investigate the IgA plasma level–mediated humoral immunity in polytrauma patients treated with GLN supplementation, showing higher IgA levels. IgA is the most abundant immunoglobulin in the human body and performs a very specialized role which involves mucosal immunity, development of tolerance and protection against infection. It is the key immunoglobulin in the respiratory and gastrointestinal tracts, which provide the first line of body defence [8].
Production of IgA is controlled by cytokine-producing T cells within the gut-associated lymphoid tissue (GALT) and possibly by cytokine released from the mucosa [9]. The two most important compartments in which IgA are located are blood and mucous secretions: in the blood, IgA is found as a monomer and is produced in the bone marrow by plasma cells that derive from B cells activated in the lymph nodes; in mucous tissues, IgA is secreted from IgA+ plasma cells after sensitization in the Peyer’s patches as a dimer, bound by a J chain, and associated with the polymeric immunoglobulin receptor. The resulting immunoglobulin is known as secretory IgA (sIgA) [10, 11]. It is well known that GLN affects intestinal production of sIgA in humans and many other mammals, such as mice, pigs, and rats, and has critical roles in intestinal homeostasis by regulating immune responses via multiple mechanisms [12,13,14].
Herein, we showed higher T and B lymphocyte levels in the GLN group. GLN appears to be fundamental in activation and proliferation of both CD3+/CD19+ B and CD3+/CD4+ and CD3+/CD8+ T lymphocytes. Specifically, it has been noticed that GLN enhances T lymphocytes’ functions, playing a crucial role in the Krebs cycle [15]. Additionally, recent data showed that T cell activation is associated with rapid GLN uptake, by an amino acid transporter, ASCT2, as well as in vitro and in vivo conditions [16].
Regarding the cytokine profile, we analysed IL-2 and IL-4, pro- and anti-inflammatory cytokines, respectively.
Concord to in vitro experiments, our results showed increased IL-2 and IL-4 levels in patients treated with GLN.
Chang et al. found that 0.6mM GLN significantly enhanced IL-2 and IL-4 levels in vitro. Furthermore, cytokine responses required the presence of optimal concentrations of GLN [11,12,13,14,15,16,17].
Another important item is the route of GLN administration (PN or EN). Although there are several reports of beneficial effects of GLN supplementation by the EN route in ICU patients [18, 19], there is always an uncertainty whether or not the patient has received the prescribed dose. In addition, the complete absorption of GLN in the upper part of the intestine leaves very little extra GLN to other tissues as almost nothing passes through the liver into the general circulation. So these are arguments that favour the GLN administration by the PN route in addition to EN [20]. For these reasons, we have chosen PN GLN supplementation in ICU polytrauma patients.
Regarding the timing and dose of GLN supplementation, our patients were treated by conventional EN enriched with 50mg/kg/IBW of intravenous GLN for 7 consecutive days, according to previous literature results. Recently, ESPEN guidelines recommend, in critically ill trauma, additional EN doses of GLN (0.2–0.3 g/kg/day) for the first 5 days with EN and in case of complicated wound healing for a longer period of 10 to 15 days [21].
This study showed a similar mortality and length of ICU stay in both polytrauma groups. However, contradictory findings have been recently reported in the literature regarding the linking between low or high GLN levels and mortality, so the debate is still open [22].
Our study showed that MV time was comparable between GLN and control groups.
Contrary, Ni et al. showed that in critical patients with acute liver injury MV time was shorter in the GLN group than in the control group but they could not claim that this result is strictly addicted to GLN supplement [23].
However, animal researches demonstrated that GLN preserved breath muscle strength and reduced tissue damage in the organs [24, 25]. Because of the retrospective nature of our study, we could not evaluate any ultrasonographic diaphragmatic measurement such as diaphragmatic inspiratory excursion, time to peak inspiratory amplitude of the diaphragm, diaphragmatic thickness (DT), DT difference, and diaphragm thickening fraction, during the study period [26].
Other limitations of our study were as follows: we could not measure GLN plasma levels, because of a lack of kits based on high-performance chromatography. It would be ideal to measure plasma glutamine levels of all patients prior to supplementation, but it is not routine practice in most clinical settings. Furthermore, we did not analyse infectious setting because of the high variability of antibiotic therapy.