Posttraumatic Inflammation is a Complex Response Based on the Pathological Expression of the Nervous, Immune, and Endocrine Functional Systems

Abstract

The successive phases that make up both the local and systemic posttraumatic acute inflammatory response could represent the expression of three concatenated pathological or "primitive" functional systems with trophic properties: the nervous, immune, and endocrine ones. The nervous functional system would play an important role in the phenomenon of ischemia-reperfusion, which would be represented by nutrition by diffusion that is either anaerobic (ischemia) or with defective use of oxygen (reperfusion) and, thus, with a limited energy requirement. The immune functional system would be represented by the infiltration of the tissues by inflammatory cells and bacteria, which would become mediators in providing nutrition to the injured tissues. Although the use of oxygen would still be defective, hypermetabolism and fever would occur. In these inflammatory response phases, the lymphatic is the most important circulation. The endocrine functional system would be the most specialized and would have high energy requirements because it would be represented by the blood capillary-mediated nutrition. Highly specialized epithelial cells would already possess a perfected oxidative metabolism. The successive expression of these three functional systems during embryonic development and also during the evolutionary development of our species could explain why the inflammatory response is a ubiquitous mechanism that is common to multiple diseases, because it is an integrator of the ontogeny and phylogeny.

“Combo” nanomedicine: Co-delivery of multi-modal therapeutics for efficient, targeted, and safe cancer therapy

“…It was suggested that systemic treatment with p53-activating chemotherapeutics might enhance antitumor responses of normal macrophages without augmenting pro-tumor functions of tumor associated macrophages (TAMS). The hypoxic nature of the TME determines the types of inflammatory cells that infiltrate, typically favoring those that depend on the glycolytic pathway for survival [125,126]. Certain phenotypes of the TAMS and neutrophils are largely associated with promoting tumor cell growth, and NF-κB signaling plays a key role in controlling these phenotypes [127].…”

“…4. Various nanoformulations for co-delivery of therapeutics with normalized pharmacokinetics and pharmacodynamics, including self-assembled nanoscale coordination polymer [158], cholesterol-based chimeric nanoparticle [157], thermosensitive hydrogel [123], mesoporous silica nanoparticle [125], and liposomes [124].…”

The use of inflammation by tumor cells

“…This type of metabolism is characterized by a large production of adenosine triphosphate (ATP), which is used to drive specialized multiple cellular processes. 7,9,10 Because the nervous, immune, and endocrine phases of the inflammatory response progress from ischemia to the development of an oxidative metabolism, it also is tempting to speculate on whether the body reproduces the successive stages by which life passes from its origin without oxygen until it develops an effective, although costly, system for the use of oxygen every time we suffer posttraumatic acute inflammation. 9,10 Likewise, the successive expression of these three functional systems during embryonic development and also during the evolutionary development of our species may explain why the inflammatory response is a ubiquitous mechanism that is common to multiple diseases, because it is an integrator of the ontogeny and phylogeny.…”

“…9,10 Likewise, the successive expression of these three functional systems during embryonic development and also during the evolutionary development of our species may explain why the inflammatory response is a ubiquitous mechanism that is common to multiple diseases, because it is an integrator of the ontogeny and phylogeny. 7 …”

“…Finally, in the late or endocrine phase, nutrition mediated by the blood capillaries is established. 7 In these three successive phases, the inflammatory response progresses from an anaerobic metabolism (ischemia), through a metabolism characterized by defective oxygen use (reperfusion, oxidative burst, and heat hyperproduction), and, finally, to an oxidative metabolism (oxidative phosphorylation) with correct use of oxygen to produce usable energy. This type of metabolism is characterized by a large production of adenosine triphosphate (ATP), which is used to drive specialized multiple cellular processes.…”