Understanding Inflammation: A Comprehensive Overview

Chronic inflammation is a prolonged immune response that occurs when the body fails to eliminate an acute infection, leading to a persistent struggle between the host and the pathogen. This type of inflammation plays a significant role in the progression of various diseases such as Alzheimer's, Parkinson's, heart disease, and metastatic cancer.

In contrast, acute inflammation is a rapid response to tissue damage, characterized by vasoconstriction, followed by vasodilation, increased vascular permeability, and visible signs of inflammation such as redness, swelling, heat, pain, and loss of function. During acute inflammation, bradykinin release causes capillary dilation, tissue swelling, and edema. An increasing number of neutrophils are recruited to fight pathogens.

One example of chronic inflammation is lymphatic filariasis, a disease caused by microscopic nematodes. Affecting approximately 120 million people worldwide, primarily in Africa and Asia, lymphatic filariasis results in the residing of adult worms in lymphatic vessels. This causes infiltration by lymphocytes, plasma cells, eosinophils, and platelets, leading to granuloma formation and obstruction of the lymphatic system.

Granulomas, nodules formed by the infiltration of white blood cells into infected tissue, are a common outcome of chronic inflammation. The cause for their formation is primarily a persistent immune reaction, often autoimmune or due to a chronic infectious stimulus. Macrophages, including epithelioid and multinucleated giant cells, aggregate locally to isolate and contain the offending agent or irritant.

Fever, an inflammatory response extending beyond the infection zone, affects the entire body and causes a general increase in body temperature. Fever is regulated and maintained by the hypothalamus, but certain bacterial or viral infections can change its "thermostat setting" through the production of pyrogenic chemicals. Pyrogens, such as endotoxin lipopolysaccharide (LPS) produced by gram-negative bacteria, can stimulate the release of endogenous pyrogens like interleukin-1 (IL-1), IL-6, interferon-γ (IFN-γ), and tumor necrosis factor (TNF). These, in turn, can trigger the release of prostaglandin E2 (PGE2) from other cells, resetting the hypothalamus and initiating a fever.

During a fever, the skin's blood vessels constrict, making the skin appear pale, and the hypothalamus triggers muscle tremors for heat production. The crisis phase of a fever involves vasodilation, allowing blood flow to return to the skin and subsequent heat loss, as well as stimulating sweating to cool the skin as the sweat evaporates.

An overly robust inflammatory response can cause tissue and organ damage, and in severe cases, even death. Superantigens, such as those produced by Staphylococcus aureus and Streptococcus pyogenes, can cause excessive activation of T cells and the excessive release of inflammatory cytokines, potentially leading to life-threatening fevers.

Tissue repair can begin in the injured area after acute inflammation. Neutrophils form an inflammatory mass consisting of dead cells, tissue fluids, and debris during acute inflammation, which is typically cleaned up by macrophages a few days later.

In summary, chronic inflammation, a persistent immune response, can lead to various health issues, with lymphatic filariasis being a prime example. Understanding the mechanisms of inflammation and its consequences is crucial for developing effective treatments and preventing the progression of related diseases.