Immune Regulating Steroid
Hormones.
e-mail: creading@holliseden.com
Immune regulating hormones
(IRH) are anti-inflammatory, immune modulating steroids, devoid of immune
suppressive or androgenic side effects. IRH show benefit in models of infectious,
metabolic, neoplastic and autoimmune diseases. IRH increase Th1 and limit
Th2 responses. Differences relate to orientation and
functionality at specific points on the steroid ring. One
synthetic IRH, HE2000 (16 a epi-androsterone) shows dramatic benefit as immune
therapy for patients with HIV/AIDS. Benefits include
significant reductions in viral loads, frequencies of opportunistic infections
(especially TB), levels of pro-inflammatory cytokines (TNF-a, IL-1b, IL-6, IL-8) and increased markers of protective immunity
(HIV specific CD8+ CTL, CD123+ DC). HE2000 improves innate immunity, and
clears parasites in patients infected with P. falciparum malaria. Benefits
depend on anti-inflammatory and immune modulating capacity. HE2000 (0.1-10 uM) dose-dependently prevents LPS induced
NO production by 24 hr cultures of RAW 264.7 cells. Treatment with HE2000,
24 hr and 1 hr before challenge, limits (>50%) numbers of neutrophils
and exudate volumes in the carageenan-induced pleurisy model of acute inflammation.
In the popliteal lymph node assay, HE2000 significantly increased CD8+ T cells,
DC, and IFN-g, but not IL-4, producing cells. Certain metabolites
of HE2000 show increased (10X) potency in in vitro and in vivo models of
acute inflammation and infectious disease. Another
natural IRH, HE2100 (3b, 17b-androstenediol) restores innate immune responsesafter radiation and chemotherapy to protect against
lethal sepsis. IRH represent a novel approach to immune therapy, simultaneously
limiting inflammation and restoring protective immune responses. With an
understanding of metabolism and structure function relationships, IRH have
the potential to address some of the most challenging and unmet medical needs
of our time.