Inflammation in Immune Dysfunction

As a function of the immune system, inflammation is involved in autoimmune conditions, when the immune response fails to balance out its attack and ends up going after itself in chronic fashion. Among autoimmune diseases, asthma is characterized by both bronchial constriction and airway inflammation. In fact, scientists increasingly hypothesize symptomatic asthma features activated mast cells (by IgE), macrophages and monocytes release IL-2, TNFa and other pro-inflammatory mediators. These cytokines can activate incoming inflammatory cells, causing inflamed lungs.

Alpha-lipoic acid's (ALA) anti-inflammatory actions appear useful in asthma. In a 2004 South Korean animal study, ALA administration significantly reduced airway hyper-responsiveness; lowered proportion of eosinophils among certain bronchial cells; significantly improved pathologic lesion scores of the lungs; reduced IgE concentrations in serum; dropped IL-4 and IL-5 concentrations in bronchial fluid; and inhibited intracellular ROS and NFkappaB DNA-binding activity.¹

Vitamins have also shown promise against airway inflammation. In 2008, University of Iowa scientists explained how active vitamin D in lung epithelial cells alters induction of antimicrobial peptides and inflammatory cytokines—mainly the NFkappaB-driven IL-8—in response to viruses.² Indiana University scientists studying exercise-induced asthma found vitamin C supplementation (1.2 g/d for two weeks) reduced inflammatory markers, such as leukotrienes, leading to improved overall lung function and asthma scores.³ Vitamin E, as alpha-tocopherol, also reduced pro-inflammatory mediators, including the cytokines IL-4 and IL-5, in a study of allergen-induced airway hyper-responsiveness and inflammation.⁴ Gamma-tocopherols have shown similar benefits.⁵

While the anti-inflammatory results from these compounds have not been clearly linked to their antioxidant properties, it appears antioxidants have a positive effect on inflammation in asthma. The citrus bioflavonoid limonene has shown anti-inflammatory effects on parameters such as diminished peribronchiolar and perivascular inflammatory infiltrates, at least in animal research.⁶

The phytochemicals in French maritime pine bark extract (as Pycnogenol®, Natural Health Sciences) are also potent antioxidants with cytokine-regulatory capability. Pycnogenol reduced ROS production by neutrophils and was deemed a good second line therapy to reduce the inflammatory feature of systemic lupus.⁷ More recently, researchers at Loma Linda University showed Pycnogenol lowered plasma levels of leukotrienes, which can cause inflammation and bronchial constriction associated with respiratory illnesses such as asthma.⁸

With such a crucial role in one inflammatory cascade, it is no surprise that increased intake of omega-3 fatty acids have been linked to improved lung function and reduced incidence of asthma;⁹ however, early work failed to connect increased omega-3 with improved asthma symptoms. Then in 2006, Indiana University researchers reported their study of exercise-induced bronchoconstriction (EIB) revealed fish oil supplementation reduced various inflammatory leukotrienes and cytokines, causing pulmonary function to improve to below the diagnostic EIB threshold, with a concurrent reduction in bronchodilator use.¹⁰

As is the nature of autoimmune-related diseases marked by hypersensitivities, some seemingly beneficial nutrients can be counterproductive. Creatine supplementation is popular among athletes, among whom prevalence of asthma is high. While creatine has shown promising benefits to certain pulmonary diseases, it has been found to exacerbate allergic lung inflammation in exercise-induced asthma.¹¹ A 2007 report out of the University of Sao Paulo, Brazil, detailed how creatine supplementation in a model of chronic allergic lung inflammation increased hyper-responsiveness, eosinophilic inflammation and airway density of IL-4, IL-5, and other inflammatory cells.

Also, folic acid is one of the mainstay vitamin supplements for expecting mothers, but for all the benefits to their children, the nutrient has one possible negative possibility. The potential detriment is in folic acid's role as a methyl donor. In a recent Duke University Medical Center, Durham, N.C., investigation, a maternal diet supplemented with methyl donors enhanced the severity of allergic airway disease that was inherited transgenerationally.¹² David Schwarts, M.D., one of the study authors, noted methyl donors include folic acid, L-methionine, choline and genistein as well as some foods high in those methyl donors, such as onions, garlic and beets.

References for "Inflammation in Immune Dysfunction"

1. Cho YS et al. "Alpha-Lipoic acid inhibits airway inflammation and hyperresponsiveness in a mouse model of asthma." J Allergy Clin Immunol. 2004 Aug;114(2):429-35.

2. Hansdottir S et al. " Respiratory epithelial cells convert inactive vitamin D to its active form: potential effects on host defense." J Immunol. 2008 Nov 15;181(10):7090-9.

3. Tecklenburg SL et al. "Ascorbic acid supplementation attenuates exercise-induced bronchoconstriction in patients with asthma." Respir Med. 2007 Aug;101(8):1770-8.

4. Okamoto N et al. " Effects of alpha tocopherol and probucol supplements on allergen-induced airway inflammation and hyperresponsiveness in a mouse model of allergic asthma." Int Arch Allergy Immunol. 2006;141(2):172-80.

5. Wagner JG et al. " Ozone enhancement of lower airway allergic inflammation is prevented by gamma-tocopherol." Free Radic Biol Med. 2007 Oct 15;43(8):1176-88

6. Keinen E et al. "Natural ozone scavenger prevents asthma in sensitized rats." Bioorg Med Chem. 2005 Jan 17;13(2):557-62.

7. Bito T et al. “Pine bark extract pycnogenol downregulates IFN-gamma-induced adhesion of T cells to human keratinocytes by inhibiting inducible ICAM-1 expression.” Free Rad Biol Med. 28, 2:219-27, 2000.

8. Lau B et al. “Pycnogenol as an adjunct in the management of childhood asthma.” J Asthma. 41, 8:825-32, 2004.

9. Wong KW et al. "Clinical efficacy of n-3 fatty acid supplementation in patients with asthma." J Am Diet Assoc. 2005 Jan;105(1):98-105.

10. Mickleborough TD et al. "Protective effect of fish oil supplementation on exercise-induced bronchoconstriction in asthma." Chest. 2006 Jan;129(1):39-49.

11. Vieira RP et al. "Creatine supplementation exacerbates allergic lung inflammation and airway remodeling in mice." Am J Respir Cell Mol Biol. 2007 Dec;37(6):660-7.

12. Schwartz DA et al. " In utero supplementation with methyl donors enhances allergic airway disease in mice." J Clin Invest. 2008 Oct;118(10):3462-9.