THE EFFECTS OF NASALLY INSTILLED VIRUS OF POLIOMYELITIS ON THE CEREBROSPINAL FLUID AND THE BLOOD OF MONKEYS
Authors: Simon Flexner
Journal: The Journal of Experimental Medicine (1935)

Macacus rhesus and Macacus cynomolgus exhibit a striking sensitivity to the presence of the virus of poliomyelitis on the nasal mucous membranes. Irrespective of whether detectable symptoms of clinical poliomyelitis do or do not arise in the nasally instilled animals, the cerebrospinal fluid changes quickly in response to virus placed in the nasal passages. Two sets of changes occur in the cerebrospinal fluid: the constant and most pronounced change consists of increase in the content of white cells, chiefly of the lymphocytic type; the inconstant and less profound one consists of detectable amounts of globulin in the fluid (free from red corpuscles) withdrawn by cisterna puncture. As early as 48 hours after instillation of the virus, a marked increase in cells is already detectable in the fluid; the increase grows from day to day, reaching a maximum sometimes in another day or two, sometimes not until 4, 5, or 6 more days elapse. In many instances a rise of temperature follows or coincides with the rising tide of cells; and the onset of clinical symptoms of disease bears also a relation to the cell count. The number of cells in the cerebrospinal fluid and the temperatures tend to be higher in monkeys which develop paralytic symptoms; occasionally exceptions to this rule occur, in which instilled monkeys remaining asymptomatic exhibit high cell counts; very rarely do the latter show the higher temperatures. Monkeys once instilled which fail to become symptomatically affected again react by cerebrospinal fluid changes to later courses of instillation. A second or still later course may induce paralysis; or highly exceptional or refractory animals may go through several courses of instillation without developing clinical symptoms, although never failing to respond with changes in the cerebrospinal fluid. The virus instillations of Macacus monkeys do not lead to active immunization unless clinical symptoms of infection have resulted from the inoculations and attended the cerebrospinal fluid changes. In the complete absence of clinical symptoms the instilled animals fail to develop blood antiviral properties, and they are as susceptible to the cerebral injection of virus as are the control monkeys. On the other hand, instilled monkeys which have shown even mild and fleeting (abortive) clinical symptoms of infection, resist cerebral inoculation and exhibit blood antiviral or neutralizing properties. Monkeys which have developed clinical symptoms of disease and have recovered are, as stated, actively immunized; they remain, however, sensitive to the presence of virus on the nasal membrane, reacting with cerebrospinal fluid changes, differing only in degree from the nonimmune animals. Detectable virus does not appear in the pleocytic cerebrospinal fluid at any stage of the pathological processes. The current belief is that mass immunization is proceeding in an unperceived manner through the chance entrance of virus into the nasal passages of children. It is not known whether, apart from all symptoms of disease, cerebrospinal fluid changes occur in the course of this unexpressed, spontaneous process. A large gap seems to exist between man and the monkey in the capacity of the former to become immunized by way of the nasal membrane, and the inability of the latter to do so. It is common knowledge that monkeys do not become immune through unsuccessful cerebral inoculations of virus, and the same seems to be true of the nasal channel of virus penetration into the central nervous organs.