Abstract
Normal or “good” inflammation process starts from a local cellular response against injury or any infectious agent, with the activation of neutrophils, macrophages, Langerhans cells, dendritic cells, and innate immune cells. Cytokines and chemokines are produced to amplify the local inflammatory process followed by the migration of immune cells to the regional lymph nodes where adaptive immune response is initiated. Systemic inflammation enhances the biological response to mobilize additional cells from central and peripheral immune/hematopoietic system. Local mechanisms to limit inflammation are initiated and lead to healing. During the normal inflammatory process, there is a balance between the production of inflammatory chemokines/cytokines such as Tumor Necrosis Factor (TNF)-α, interleukin (IL)-6 and IL-1 and the production of compounds that limit inflammation and have an immune suppressive effect, such as IL-10 and Transforming Factor (TGF) β. IL-6 and IL-6/soluble IL-6 Receptor (R) complex stimulate liver cells to produce inflammatory proteins, which represents the systemic inflammation response. The magnitude and the duration of the systemic inflammatory response are linked to the cause, under genetic and epigenetic control. Significant inflammation as seen in septic shock, in severe forms of infections or in certain active cancers, represents the “bad inflammation”, correlated with a poor prognosis. In addition, the persistence of a chronic smoldering inflammation may lead to pathological situations which are observed in the majority of inflammatory, degenerative, dysmetabolic, or dysimmune diseases and cancer. Chronic smoldering inflammation is a cross between different pathological situations possibly linked. In addition, within the tumor microenvironment, inflammatory process results from different cellular mechanisms modulated by metabolic and vascular changes. On the contrary, a limited and balanced inflammation initiates the normal immune response, including the adaptive response which amplifies any immunotherapy, including vaccines. Immune checkpoint inhibitors and chimeric antigen receptor (CAR) T-cells are associated with cytokine release syndrome, a clinical risk leading to the use of anti-cytokine drugs. Nowadays, it is time to monitor the dynamic inflammatory process for a better immune precision medicine in both infections and cancer.
Highlights
Inflammation is an essential and normal biological mechanism for response to an injury in humans
In the late 19th century, inflammation associated to infection and the germ theory of disease was introduced by Robert Koch and Louis Pasteur
Intravascular migration of neutrophils starts by “rolling” on the endothelium of blood vessels which is mediated by selectins and followed by chemokine activation through a conformational change of the G protein coupled receptor leading to activation of neutrophil integrins such as very late antigen (VLA)-4 (CD49D/CD29), macrophage-1 antigen (MAC1, CD11b/CD18), and lymphocyte function-associated antigen 1 (LFA-1, CD11a/CD18) [39]
Summary
Inflammation is an essential and normal biological mechanism for response to an injury in humans. The favorable anticancer immune response observed in a particular patient having mantle cell lymphoma with poor prognosis was associated with a transient and limited inflammatory response This observation illustrates a good inflammatory response which is the beginning of an adaptive immune response, both at cellular and humoral response levels. The presence of a smoldering chronic inflammation, described in the process of aging named inflammaging, as observed with congestive heart failure or chronic pulmonary disease, greatly reduces the specific immune response as demonstrated with varicella-zoster vaccine [9, 10]. This lowlevel of persistent chronic inflammation has been observed to be associated with generalized atherosclerosis and used for cardiovascular risk stratification [11, 12]
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