Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 Dec 22:12:761382.
doi: 10.3389/fimmu.2021.761382. eCollection 2021.

Role of Exercise Intensity on Th1/Th2 Immune Modulations During the COVID-19 Pandemic

Affiliations
Review

Role of Exercise Intensity on Th1/Th2 Immune Modulations During the COVID-19 Pandemic

Rashmi Supriya et al. Front Immunol. .

Abstract

The COVID-19 pandemic has led to several pioneering scientific discoveries resulting in no effective solutions with the exception of vaccination. Moderate exercise is a significant non-pharmacological strategy, to reduce the infection-related burden of COVID-19, especially in patients who are obese, elderly, and with additional comorbidities. The imbalance of T helper type 1 (Th1) or T helper type 2 (Th2) cells has been well documented among populations who have suffered as a result of the COVID-19 pandemic, and who are at maximum risk of infection and mortality. Moderate and low intensity exercise can benefit persons at risk from the disease and survivors by favorable modulation in Th1/Th2 ratios. Moreover, in COVID-19 patients, mild to moderate intensity aerobic exercise also increases immune system function but high intensity aerobic exercise may have adverse effects on immune responses. In addition, sustained hypoxia in COVID-19 patients has been reported to cause organ failure and cell death. Hypoxic conditions have also been highlighted to be triggered in COVID-19-susceptible individuals and COVID-19 survivors. This suggests that hypoxia inducible factor (HIF 1α) might be an important focus for researchers investigating effective strategies to minimize the effects of the pandemic. Intermittent hypoxic preconditioning (IHP) is a method of exposing subjects to short bouts of moderate hypoxia interspersed with brief periods of normal oxygen concentrations (recovery). This methodology inhibits the production of pro-inflammatory factors, activates HIF-1α to activate target genes, and subsequently leads to a higher production of red blood cells and hemoglobin. This increases angiogenesis and increases oxygen transport capacity. These factors can help alleviate virus induced cardiopulmonary hemodynamic disorders and endothelial dysfunction. Therefore, during the COVID-19 pandemic we propose that populations should engage in low to moderate exercise individually designed, prescribed and specific, that utilizes IHP including pranayama (yoga), swimming and high-altitude hiking exercise. This would be beneficial in affecting HIF-1α to combat the disease and its severity. Therefore, the promotion of certain exercises should be considered by all sections of the population. However, exercise recommendations and prescription for COVID-19 patients should be structured to match individual levels of capability and adaptability.

Keywords: COVID-19; Th1/Th2 ratio; hypoxia; immunomodulation; intermittent hypoxic preconditioning.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Summary of Naive T (T0) cells differentiation in (A) T helper 1 (Th1) cells due to the surrounding microenvironment of IL-12 and further secretes IL-2 and IFN-ϒ and activates macrophage and causes inflammation, (B) T helper 2 (Th2) cells due to the surrounding microenvironment of IL-4 and further secretes IL-4, IL-5, IL-13 and activates eosinophil and B cells, (C) T helper 17 (Th17) cells due to the surrounding microenvironment of IL-6 and TGF-β and further secretes IL-17, IL-22 to recruit neutrophils and causes inflammation, (D) T regulatory (Treg) cells that secretes IL-10, TGF-β and suppresses immune response, (E) Follicular helper T (TFH) cells and secretes IL-21, and guide B cells to produce antibodies. IL is interleukins, TGF-β is Transforming growth factor-β and a B cell is B lymphocytes.
Figure 2
Figure 2
Moderate to low intensity exercise upregulates Th1 and downregulates Th2 in people susceptible to COVID-19 infection (including obese, elderly and people with other comorbidities), COVID-19 patients and COVID-19 survivors with upregulated Th2 and downregulated Th1. Th1 is T helper cells 1 and Th2 is T helper cells 2.
Figure 3
Figure 3
Expected mechanism proposed in COVID-19 era. (A) HIF-1 α is already exacerbated in obese people and it might further exacerbates ACE in pulmonary smooth cells and circulation making the obese more susceptible to COVID-19 infection, (B) HIF-1 α is already exacerbated in people with other comorbidities and it might further exacerbates VEGF, iNOS, EPO, inhibits fatty acid B oxidation, produces cellular reactive oxygen species making the people with other comorbidities more susceptible to COVID-19 infection, (C) HIF-1 α is already exacerbated in elderly people it further reduces mitochondrial encoded protein including SIRT1 gene making the elderly people more susceptible to COVID-19 infection, (D) HIF-1 α is vital regulator of steroidenesis and it leads to shift towards glycolysis and reduces nutrition in brain affecting neurotransmitters that may be the reason behind stress depression and anxiety among COVID-19 survivors, interaction between (E) NFkβ and HIF-1α might be the reason behind sustained hypoxia in COVID-19 patients promoting Th17, Th1, Th2 and suppressing Treg cells. HIF-1 α is hypoxia induced factor 1 alpha, Th is T helper cells, ACE is Angiotensin-converting enzyme, VEGF is Vascular endothelial growth factor, iNOS is inducible nitric oxide synthase, EPO is Erythropoietin, SIRT1 is Sirtuin 1, NFkβ is nuclear factor kappa-light-chain-enhancer of activated B cells, RORϒT is Retineic-acid-receptor-related orphan nuclear receptor gamma, IFNϒ is interferon gamma, FoXP3 is forkhead box P3.
Figure 4
Figure 4
Exercise that involves intermittent hypoxic preconditioning might be the solution for all populations who are at highest risk of infection and mortalities during the COVID-19 pandemic. It decreases cortisol levels, increases catecholamine levels, increases nutrition in brain modulating neurotransmitters, increases VEGF, iNOS, EPO, increases mitochondrial encoded protein including SIRT1 gene, inhibits over activated immune system, activates fatty acid β oxidation and reduces ACE2. ACE is Angiotensin-converting enzyme, VEGF is vascular endothelial growth factor, iNOS is inducible nitric oxide synthase, EPO is Erythropoietin, SIRT1 is Sirtuin 1.

Similar articles

Cited by

References

    1. Röcken M, Müller KM, Saurat JH, Hauser C. Lectin-Mediated Induction of IL-4-Producing CD4+ T Cells. J Immunol (1991) 146:577–84. - PubMed
    1. Sad S, Mosmann TR. Single IL-2-Secreting Precursor CD4 T Cell Can Develop Into Either Th1 or Th2 Cytokine Secretion Phenotype. J Immunol (1994) 153:3514–22. - PubMed
    1. Szulc B, Piasecki E. Effects of Interferons, Interferon Inducers and Growth Factors on Phagocytosis Measured by Quantitative Determination of Synthetic Compound Ingested by Mouse Bone Marrow-Derived Macrophages. Arch Immunol Ther Exp (Warsz) (1988) 36:537–45. - PubMed
    1. Livingston DH, Appel SH, Sonnenfeld G, Malangoni MA. The Effect of Tumor Necrosis Factor-α and Interferon-γ on Neutrophil Function. J Surg Res (1989) 46:322–6. doi: 10.1016/0022-4804(89)90195-9 - DOI - PubMed
    1. Diamond RD, Lyman CA, Wysong DR. Disparate Effects of Interferon-Gamma and Tumor Necrosis Factor-Alpha on Early Neutrophil Respiratory Burst and Fungicidal Responses to Candida Albicans Hyphae In Vitro . J Clin Invest (1991) 87:711–20. doi: 10.1172/JCI115050 - DOI - PMC - PubMed

Publication types