Soluble Mediators Regulating Immunity in Early Life

Abstract

Soluble factors in blood plasma have a substantial impact on both the innate and adaptive immune responses. The complement system, antibodies, and anti-microbial proteins and peptides can directly interact with potential pathogens, protecting against systemic infection. Levels of these innate effector proteins are generally lower in neonatal circulation at term delivery than in adults, and lower still at preterm delivery. The extracellular environment also has a critical influence on immune cell maturation, activation, and effector functions, and many of the factors in plasma, including hormones, vitamins, and purines, have been shown to influence these processes for leukocytes of both the innate and adaptive immune systems. The ontogeny of plasma factors can be viewed in the context of a lower effectiveness of immune responses to infection and immunization in early life, which may be influenced by the striking neonatal deficiency of complement system proteins or enhanced neonatal production of the anti-inflammatory cytokine IL-10, among other ontogenic differences. Accordingly, we survey here a number of soluble mediators in plasma for which age-dependent differences in abundance may influence the ontogeny of immune function, particularly direct innate interaction and skewing of adaptive lymphocyte activity in response to infectious microorganisms and adjuvanted vaccines.

High expression levels of macrophage migration inhibitory factor sustain the innate immune responses of neonates

“…This parallels the postnatal fall in circulating concentrations of cortisol, placental steroids, prostaglandins, and adenosine, which are potent inhibitors of neonatal innate immune responses (9)(10)(11)(12)46). The expression pattern of MIF in newborns is unique in the sense that MIF reaches blood levels that are at least 10-fold higher than those measured in healthy children and adults, an observation that has no antecedent for a proinflammatory cytokine or mediator (7,13). Circulating MIF levels in healthy-term newborns are in fact comparable to those of children and adults with septic shock (23,26).…”

“…Soluble factors in blood influence immune responses (6)(7)(8). Notably, adenosine, prostaglandins, cortisol, estradiol, and progesterone are present at high circulating concentrations perinatally and have the ability to reduce the production of proinflammatory cytokines by neonatal innate immune cells exposed to microbial products (9)(10)(11)(12)(13).…”

Waning Immunity and Microbial Vaccines—Workshop of the National Institute of Allergy and Infectious Diseases

“…Key to the in vitro modeling approach are the use of human systems that are age specific and include autologous human plasma, which is a rich source of age-specific immunomodulatory factors (84), the use of primary leukocytes and epigenetic programs, and avoiding the use of exogenous cytokines or heat-treated conditions. The use of in vitro systems that model soluble (plasma) and cellular age-specific human immune responses and the systems biology ("omics") approaches to biomarker and pathway discovery have enabled (i) the identification of age-specific adjuvants/adjuvant combinations to inform targeted adjuvanted vaccine development (85) and (ii) the benchmarking of new versus licensed vaccines to accelerate age-specific vaccine development.…”

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“…Показано, что для новорожденных детей характерен относительно повышенный уровень содержания IL 6, IL 10 в сочетании с относительно сниженным уровнем кон центрации большинства провоспалительных цитокинов, компонентов комплемента, антимикробных пептидов [46].…”

“…Сравнение содержания цитокинов, комплемента, антимикробных пептидов, иммуноглобулинов у доношенных и недоношенных новорожденных [46] ISSN 1992 5913 Современная педиатрия 3(75)/2016…”