Immune Metabolism in TH2 Responses: New Opportunities to Improve Allergy Treatment — Disease-Specific Findings (Part 1)

Abstract

Purpose of Review Recent high-level publications have shown an intricate connection between immune effector function and the metabolic state of the respective cells. In the last years, studies have begun analyzing the metabolic changes associated with allergies. As the first part of a two-article series, this review will briefly summarize the basics of immune metabolism and then focus on the recently published studies on metabolic changes observed in allergic patients. Recent Findings In the last 3 years, immune-metabolic research in allergology had a clear focus on asthma with some studies also reporting findings in food allergy and atopic dermatitis. Current results suggest asthma to be associated with a shift in cellular metabolism towards increased aerobic glycolysis (Warburg metabolism), while also displaying substantial changes in fatty acid- and amino acid metabolism (depending on investigated patient collective, asthma phenotype, and disease severity). Summary Understanding immune-metabolic changes in allergies will allow us to (I) better understand allergic disease pathology and (II) modulate immune-metabolic pathways to improve allergy treatment.

Metabolomic analysis of the effect of endocannabinoid metabolism inhibition in ovalbumin-induced allergic airway inflammation in Guinea pigs

“…Metabolism represents a highly intricate and multifaceted network of biochemical reactions, which are orchestrated with the purpose of endowing the cell with the appropriate molecules at the appropriate moment. To expound, the intricate process of metabolism involves the breakdown of glucose, fatty acids, and amino acids with the intention of generating both energy in the form of ATP and metabolites that serve as the essential building blocks of various cellular pathways and components (14). To meet the energy demands of cellular processes, glucose undergoes a complex enzymatic process called glycolysis, consisting of multiple sequential reactions that yield two molecules of pyruvate and two molecules of ATP.…”

“…This selective catabolism of glucose to lactate is known to disrupt the Krebs cycle, as a consequence of inadequate pyruvate supply to the mitochondria. This impairment leads to specific arrest points in the Krebs cycle, which consequently results in the accumulation of intermediary metabolites (14). For example, research on macrophages stimulated with LPS has revealed that these arrest points occur downstream of citrate and succinate (21, 22).…”

“…Furthermore, immune cell metabolism not only maintains the energy needs of activated cells but also plays a critical role in the synthesis of essential immunological effector molecules. Therefore, comprehending the metabolic alterations in immune cells during activation is fundamental to gain insights into the pathogenesis of inflammatory diseases and to identify potential immune-metabolic pathways to modulate for improved therapeutic outcomes or enhanced biomarker discovery (14, 15). The analysis of metabolites produced in cells during metabolic processes, referred to as metabolomics, is a valuable approach in studying and investigating low-molecular weight constituents.…”

S100A8/9 modulates perturbation and glycolysis of macrophages in allergic asthma mice

“…Over the past three years, immune metabolism studies in allergies have found that asthma is associated with increased aerobic glycolysis ( Goretzki et al, 2023 ). A study of serum lactate acid levels in clinically stable patients with allergic asthma, healthy controls, and patients with chronic obstructive pulmonary disease (COPD) found that its content was substantially higher in patients than in healthy controls, which was also significantly higher than that in controls of patients with COPD ( Ostroukhova et al, 2012 ) suggesting an increase in glycolysis.…”

General Anesthesia in Early Childhood Significantly Reduces Asthma Incidence and Clinical Visits: A Nationwide Population-Based Cohort Study

“…Asthma is a chronic inflammatory process of the lower respiratory airways and a Type 2-high (Th2) disease [ 35 ]. Some researchers believe that GA may be involved in immune function by affecting the balance of Th1 and Th2 in favor of Th1 responses [ 36 ] or stress responses caused by surgery [ 37 ].…”