Page 192 - Veterinary Immunology, 10th Edition

VetBooks.ir Systemic Innate Responses

Hematopoietic stem cells (HSCs) respond to systemic infections as
the body needs to replenish its supply of neutrophils and

macrophages. This response is mediated by many cytokines,
including granulocyte colony-stimulating factor as described in
Chapter 5. Inflammation-associated cytokines such as interferons
and TNF-α also have a direct effect on HSCs and stimulate them to
proliferate. Since HSCs express TLR2 and TLR4, bacterial PAMPs

such as lipopolysaccharides also promote their proliferation and an
elevated white cell count.

Metabolic Changes

In addition to causing a fever, inflammatory cytokines, especially
IL-1, promote the release of sleep-inducing molecules. Thus
lethargy is commonly associated with a fever. This response may
reduce other energy demands of an animal, and increase that

available for defense and repair.
IL-1, IL-18, and leptin also suppresses the hunger centers in the
hypothalamus and so are responsible for the loss of appetite
associated with infections. The benefits of this are unclear, but it

may permit the animal to be more selective about its food
IL-1, IL-6, and TNF-α also act on skeletal muscle to increase
protein catabolism and release amino acids. Although this
eventually results in myalgia and muscle wastage, the newly

available amino acids are available for increased antibody and
cytokine synthesis. If animals are subjected to long-term, low-grade
inflammation, they will be exposed to chronic, low doses of TNF-α.
Αs a result, they lose weight and become anemic and protein

depleted. TNF-α inhibits the uptake of lipids by preadipocytes and
causes mature adipocytes to lose stored lipids. TNF-α is thus
responsible for the weight loss seen in animals with cancer or
chronic parasitic and bacterial diseases. Weight loss is a common

response to infection (and sometimes to vaccination) and is of
special significance to livestock producers.

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