Polyinosinic:polycytidylic acid (poly I:C) is a synthetic double-stranded RNA that is used experimentally to model viral infections in vivo. Previous studies investigating the inflammatory properti...

The viral mimic, polyinosinic:polycytidylic acid, induces fever in rats via an interleukin-1-dependent mechanism

A comlex of polyriboinosinic-polyribocytidylic acid (poly I-poly C) with poly-L-lysine and carboxymethylcellulose has been prepared. This complex is five to 10 times as resistant to hydrolysis by primate serum as the parent poly I-poly C. It has a thermal denaturation temperature about 40 C higher than that of poly I-poly C. The complex induces significant levels of serum interferon in monkeys and chimpanzees under conditions in which poly I-poly C itself induces no interferon.

A modified polyriboinosinic-polyribocytidylic acid complex that induces interferon in primates.

Hair loss can be a psychologically devastating adverse effect of chemotherapy, but satisfactory management strategies for chemotherapy-induced alopecia remain elusive. In this Review we focus on the complex pathobiology of this side-effect. We discuss the clinical features and current management approaches, then draw upon evidence from mouse models and human hair-follicle organ-culture studies to explore the main pathobiology principles and explain why chemotherapy-induced alopecia is so challenging to manage. P53-dependent apoptosis of hair-matrix keratinocytes and chemotherapy-induced hair-cycle abnormalities, driven by the dystrophic anagen or dystrophic catagen pathway, play important parts in the degree of hair-follicle damage, alopecia phenotype, and hair-regrowth pattern. Additionally, the degree of hair-follicle stem-cell damage determines whether chemotherapy-induced alopecia is reversible. We highlight the need for carefully designed preclinical research models to generate novel, clinically relevant pointers to how this condition may be overcome.

Pathobiology of chemotherapy-induced hair loss

Maturation of dendritic cells (DC) to competent APC is essential for the generation of acquired immunity and is a major function of adjuvants. dsRNA, a molecular signature of viral infection, drives DC maturation by activating TLR3, but the size of dsRNA required to activate DC and the expression patterns of TLR3 protein in DC subsets have not been established. In this article, we show that cross-priming CD8α(+) and CD103(+) DC subsets express much greater levels of TLR3 than other DC. In resting DC, TLR3 is located in early endosomes and other intracellular compartments but migrates to LAMP1(+) endosomes on stimulation with a TLR3 ligand. Using homogeneous dsRNA oligonucleotides (ONs) ranging in length from 25 to 540 bp, we observed that a minimum length of ∼90 bp was sufficient to induce CD86, IL-12p40, IFN-β, TNF-α, and IL-6 expression, and to mature DC into APC that cross-presented exogenous Ags to CD8(+) T cells. TLR3 was essential for activation of DC by dsRNA ONs, and the potency of activation increased with dsRNA length and varied between DC subsets. In vivo, dsRNA ONs, in a size-dependent manner, served as adjuvants for the generation of Ag-specific CTL and for inducing protection against lethal challenge with influenza virus when given with influenza nucleoprotein as an immunogen. These results provide the basis for the development of TLR3-specific adjuvants capable of inducing immune responses tailored for viral pathogens.

TLR3-Specific Double-Stranded RNA Oligonucleotide Adjuvants Induce Dendritic Cell Cross-Presentation, CTL Responses, and Antiviral Protection

Maternal Inflammation and Neurodevelopmental Programming: A Review of Preclinical Outcomes and Implications for Translational Psychiatry.

Studies on poly I:C toxicity in experimental animals.

ADMINISTRATION of antitumour agents to patients is frequently followed by loss of hair. This loss is usually reversible in the sense that new hair replaces that lost, often during continued therapy. These changes have been noted following the administration of a variety of anti-tumour agents including Cyclophosphamide, colcemid, methotrexate, hydroxyurea, vinblastine and vincristine, which have in common the following attributes: (1) they are effective in the therapy of neoplastic disease in humans and experimental animals; (2) they frequently cause alopecia in humans; and (3) they do not cause similar alopecia in conventional laboratory animals. Cyclophosphamide was used in the work described here because of the relative prominence of its alopecic property.

Robert P. Zendzian

Papers

Studies on poly I:C toxicity in experimental animals.

Loss of hair in experimental animals induced by cyclophosphamide.

Hemostatic toxicity of poly I-C