Table 1. Types of evidence implicating nitric oxide/peroxynitrite in MCSa

1. Several organic solvents thought to be able to induce MCS, formaldehyde, benzene, carbon tetrachloride, and certain organochlorine pesticides all induce increases in nitric oxide levels.
2. A sequence of action of organophosphate and carbamate insecticides is suggested whereby they may induce MCS by inactivating acetylcholinesterase and thus produce increased stimulation of muscarinic receptors, which are known to produce increases in nitric oxide.
3. Evidence for induction of inflammatory cytokines by organic solvents that induce the inducible nitric oxide synthase (iNOS). Elevated cytokines are an integral part of the proposed feedback mechanism of the elevated nitric oxide/peroxynitrite theory (28) .
4. Neopterin, a marker of the induction of the iNOS, is reported to be elevated in MCS.
5. Increased oxidative stress has been reported in MCS; antioxidant therapy may produce improvements in symptoms, as expected if the levels of oxidant peroxynitrite are elevated.
6. In a series of studies of a mouse model of MCS involving partial kindling and kindling, excessive NMDA activity and nitric oxide synthesis were shown to be required to produce the characteristic biological response.
7. The symptoms exacerbated on chemical exposure are similar to the chronic symptoms of CFS (1) ; these may be explained by several known properties of nitric oxide, peroxynitrite, and inflammatory cytokines, each of which have a role in the proposed mechanism (30) .
8. These conditions (CFS, MCS, FM, and PTSD) are often treated through intramuscular injections of vitamin B-12; B-12 in the form of hydroxocobalamin is a potent nitric oxide scavenger in vitro and in vivo (29) .
9. As discussed below, peroxynitrite is known to induce increased permeabilization of the blood–brain barrier; such increased permeabilization is reported in a rat model of MCS.
10. Five types of evidence implicate excessive NMDA activity in MCS, an activity known to increase nitric oxide and peroxynitrite levels (see text below).

a Evidence for this list is discussed in ref 26 except as indicated by specific references listed in the table.