In vitro Production of IL-6 and IFN-γ is Influenced by Dietary Variables and Predicts Upper Respiratory Tract Infection Incidence and Severity Respectively in Young Adults

Abstract

Assessment of immune responses in healthy adults following dietary or lifestyle interventions is challenging due to significant inter-individual variability. Thus, gaining a better understanding of host factors that contribute to the heterogeneity in immunity is necessary. To address this question, healthy adults [n = 36, 18–40 years old, body mass index (BMI) 20–35 kg/m2] were recruited. Dietary intake was obtained via 3-day dietary recall records, physical activity level was evaluated using the International Physical Activity Questionnaire, and peripheral blood mononuclear cells were isolated from peripheral blood. Expression of activation markers on unstimulated immune subsets was assessed by flow cytometry. T-cell proliferation and cytokine secretion was assessed following in vitro stimulation with anti-CD3 or lipopolysaccharide. Furthermore, the incidence and severity of cold or flu symptoms were obtained from self-reported upper respiratory tract infection (URTI) questionnaires. The relationship between activation marker expression on T cells and T-cell effector functions; and in vitro cytokine secretion and URTI was determined by linear or logistic regression. CD69 and CD25 expression on unstimulated T cells was significantly associated with T-cell proliferation and interleukin-2 secretion. Incidence and severity of cold or flu symptoms was significantly associated with in vitro interleukin-6 and interferon-gamma secretion, respectively. Furthermore, host factors (e.g., age, BMI, physical activity, and diet) contributed significantly to the relationship between activation marker expression and T-cell effector function, and cytokine secretion and cold and flu status. In conclusion, these results suggest that lifestyle and dietary factors are important variables that contribute to immune responses and should be included in human clinical trials that assess immune endpoints.

Downstream mediators of the intratumoral interferon response suppress antitumor immunity, induce gemcitabine resistance and associate with poor survival in human pancreatic cancer

“…Importantly, the source of IFN γ within the tumor is likely multifactorial, as a variety of innate immune cells are capable of secreting IFN γ in response to damage or pathogen-associated molecular patterns. Further, comparable levels of IFN γ secretion as those used here have been demonstrated following lymphocyte activation [22–24]. Regardless of the source of IFN γ , the secretion of high levels of CXCL10 represents a consistent type II interferon response present in both PC cells and TAS, which likely contributes to the high levels of CXCL10 observed in PC specimens compared to nonmalignant controls.…”

“…1 × 10 5 of HPDE, PANC1, L3.6pl, PPCE and TAS were plated in 24-well culture dishes, allowed to adhere overnight and stimulated with 20 ng/ml of IFN γ (R&D Systems) for 48 h. IFN γ dosing was selected based on previous investigations evaluating T cell secretory responses following anti-CD3 stimulation [22–24] as well as our own data demonstrating approximately 20 ng/mL of IFN γ secreted by peripheral blood mononuclear cells in response to anti-CD3/CD28 stimulation at 24 h (Supplemental Fig. S1e).…”

Consumption of Bifidobacterium animalis subsp. lactis BB‐12 impacts upper respiratory tract infection and the function of NK and T cells in healthy adults

“…At baseline and after each 4‐week treatment period, participants had a blood sample collected after a 12‐h overnight fast by venipuncture at the CRC on the University Park campus. Blood (50 mL) was collected in sterile EDTA (K2)‐coated blood tubes (BD Biosciences, San Jose, CA, USA) and PBMCs were isolated as previously described .…”

“…PBMCs (2 × 10 6 /mL) were incubated with 0 or 1 μg/mL plate‐bound purified mouse anti‐human CD3 antibody (Life Technologies) in flat‐bottomed 96‐well plates and lymphocyte proliferation was assessed as previously described . Each assay was performed in triplicate.…”

“…Age, gender, BMI, PA, dietary factors, and their interactions with treatment were included as covariates. Dietary factors were selected based on their individual contributions to T‐cell and NK‐cell function at baseline . The covariates in each of the models varied depending on the immune outcome, and were selected based on manual backward selection procedure.…”