Cholesterol and infection

Question 1

Main pathogenic factor of gram neg bacteria?

Answer 1

Lipopolysaccharide or endotoxin

Question 2

What is the toxin from most pathogenic strains of Staphylococcus aureus?

Answer 2

Alpha-Toxin

Question 3

What does LDL to prevent infection?

Answer 3

• Binds rapidly to the endotoxin –> lipoprotein-bound endotoxin is unable to active the secretion of cytokines
• Binds and almost totally inactivates Alpha-Toxin

Question 4

What do you see in hypocholesterolemic individuals?

Answer 4

Fewer circulating lymphocytes, total T-cells, helper T-cells and CD8+ cells

Question 5

What has been observed in hypercholesterolemic individuals?

Answer 5

Increased: adhesiveness to cell surfaces, phagocytic activity and spontaneous motility of mononuclear cells

Question 6

What happens to total cholesterol (TC) during acute infections?

Answer 6

Synthesis increases and rate of disappearance of TC from plasma increases as well, TC levels may be up or down

Question 7

Situations less likely to happen with higher levels of TC (inverse association)?

Answer 7

• Mortality from respiratory and GI diseases
• Admission to hospital due to an infectious disease
• Admission to hospital due to Pneumonia or Influenza
• Women: UTI, GU inf, miscellaneous viral inf
• Men: UTI, musculo-skeletal inf and skin/subcutaneous inf

Question 8

TC and HIV infection, what are the inverse associations?

Answer 8

• The lower the level, the higher the risk of infection

- The lower the level, the higher the risk of death in AIDS patients

Question 9

TC and congestive heart failure (CHF)

Answer 9

Low TC –> impaired perioperative and long term survival (can have elevated plasma levels of bacterial lipopolysaccharide)

Question 10

TC and postoperative abdominal infections

Answer 10

Low TC –> higher mortality from them

Question 11

TC and Hep B infection

Answer 11

Low TC - higher risk to become chronic carrier of hep B surface antigen
Low TC - prevents eradication of Hep B inf

Question 12

What is Smith-Lemli-Opitz syndrome?

Answer 12

Inborn error of metabolism –> defective TC synthesis (deficiency 7-dehydrocholesterol reductase) –> very low TC –> many stillborn or die early from multiple malformations, those who survive –> frequent/severe inf (more evidence –> anti-infectious effects of high TC)

Question 13

What is the defect in Familial Hypercholesterolemia (FH)?

Answer 13

LDL receptor deficiency –> Very high LDL-C and TC

Question 14

What is the main point of the LDL receptor hypothesis?

Answer 14

Patients w/ FH have a greater risk of dying from coronary heart disease (CHD) at an early age

Question 15

What are the problems of the LDL receptor hypothesis?

Answer 15

Size of the risk from CHD is not certain, most studies available were done w/ selected FH patients: existing heart disease or + family Hx heart disease, mortality numbers may be even lower for unselected patients, and may be related to environmental factors rather than elevated cholesterol levels

Question 16

In what kind of individuals high TC is a risk factor for CHD?

Answer 16

Young and middle aged men (not in both sexes, all populations and all age groups)

Question 17

TC and mortality

Answer 17

In many populations the association is absent or inverse, increasing TC: low coronary and total mortality, high TC/LDL-C: does not predict CHD or all-cause mortality

Question 18

What may explain the inverse association between high cholesterol and total mortality?

Answer 18

Effects of cholesterol on the immune system. A possible increase in mortality from cardiovascular diseases may be counterbalanced by a lower mortality from infectious diseases

Question 19

Why high TC could be a risk factor for CHD in young and middle aged men?

Answer 19

In these patients high cholesterol might reflect the presence of factors promoting CHD, which might outweigh the beneficial effects

Question 20

What factors might be present in young and middle aged men that can favor CHD?

Answer 20

• Mental stress: well known cause of high cholesterol

- Adrenal hyperfunction, for which high cholesterol might be a marker

Question 21

Why does high cholesterol may predict longevity rather than mortality?

Answer 21

High cholesterol may be protective, rather than promoting atherosclerosis, possibly due to its beneficial influence on the immune system