Intradermal LPS and Antibiotics

7 day pre-treatment with erythromycin and clindamycin applied twice daily on marked area on left (erythromycin) and right side (clindamycin) of the volar lower arm. Erythromycin is a bacteriostatic antibiotic that belongs to the macrolide group of antibiotics. Macrolides act as bacteriostatic by reversibly binding to the P site on the 50S subunit of bacterial ribosomes. A topical gel formulation with hyprolose and ethanol.

7 day pre-treatment with erythromycin and clindamycin applied twice daily on marked area on left (erythromycin) and right side (clindamycin) of the volar lower arm. Clindamcin is a bacteriostatic antibiotic that belongs to the lincosamide group of antibiotics. Lincosamides act as bacteriostatic by reversibly binding to the P site on the 50S subunit of bacterial ribosomes. A topical lotion formulation with ethanol.

2 day pre-treatment with prednisolone daily dose 0.5mg/kg (0.25mg/kg in the morning and 0.25mg/kg in the evening). Prednisolone tablet (0.5mg/kg; parallel comparison): Prednisolone is a synthetic corticosteroid with predominant glucocorticoid activity and as such it is widely used in the treatment for inflammatory and autoimmune diseases. Prednisolone exerts its effect by binding to cytoplasmic glucocorticoid receptors and subsequently activates glucocorticoid receptor mediated gene expression. This results in synthesis of certain anti-inflammatory proteins, while inhibiting the synthesis of certain inflammatory mediators.

"2 day pre-treatment with clobetasol propionate 0.05% topical formulation applied twice daily on marked area on left or right side of the volar lower arm.~Clobetasol propionate 0.05% topical formulation (crossover comparison):~Clobetasol propionate is a potent synthetic corticosteroid with anti-inflammatory, anti-pruritic, and vasoconstrictive properties. Clobetasol propionate exerts its effect by binding to cytoplasmic glucocorticoid receptors and subsequently activates glucocorticoid receptor mediated gene expression. This results in synthesis of certain anti-inflammatory proteins, while inhibiting the synthesis of certain inflammatory mediators. Specifically, clobetasol propionate appears to induce phospholipase A2 inhibitory proteins, thereby controlling the release of the inflammatory precursor arachidonic acid from membrane phospholipids by phospholipase A2."

As TLR4 agonist, purified lipopolysaccharide prepared from Escherichia Coli: 113: H10:K negative (U.S. Standard Reference Endotoxin) will be used. This LPS batch is manufactured in the US by the National Institute of Health (NIH). Subjects will receive two intradermal doses of LPS in each forearm on day 0 (4 LPS injections in total, except for subjects 1-6 who receive none and subjects 25-27 will receive 2 LPS injections, only in the right arm). The dose per injection is 10 ng.