Interleukin 4 reduces the severity of clinical symptoms during the early phase of amyotrophic lateral sclerosis (ALS), but has no effect in halting the death of motor neuron cells as ALS progresses, an Italian mouse study shows.
The study, “Interleukin 4 modulates microglia homeostasis and attenuates the early slowly progressive phase of amyotrophic lateral sclerosis,” appeared in the journal Cell Death & Disease.
Activation of microglia, the central nervous system’s innate immune cells, is a hallmark of ALS and other neurodegenerative diseases. As such, therapies that modulate microglia cell activation may help prevent motor neuron cell degeneration in ALS.
Previous studies showed that the molecule interleukin IL-4 had a neuroprotective effect in animal models of multiple sclerosis, brain ischemia and spinal cord injury. It can also regulate brain function and support the formation of nerve cells and oligodendrocytes — highly specialized cells whose function is to produce the myelin layer that protects neurons.
Its role in ALS, however, remains unknown.
With that in mind, researchers at the Institute of Experimental Neurology of Italy’s San Raffaele Scientific Institute in Milan injected IL-4 into the central nervous system of mice. That activated microglia cells in the animals’ spinal cord, but induced a pattern of slow proliferation.
A deeper analysis of these cells’ gene expression showed that microglia treated with IL-4 expressed a larger number of genes normally found in embryonic microglia cells.
“Since embryonic microglia sustain CNS [central nervous system] development, we then hypothesized that turning adult microglia to acquire such phenotype via IL-4 might be an efficient in vivo strategy to sustain motor neuron survival in ALS,” researchers wrote.
They tested the effects of IL-4 therapy in the SOD1 G93A mice, an animal model of ALS.
IL-4 reduced levels of pro-inflammatory factors and increased locomotion. However, this only happened only during the early gradual phase of the disease. It did not extend survival of the mice, nor did it stop neurodegeneration in the late and fast-progressing phase of the disease.
These results, concluded researchers, suggest that “the anti-inflammatory action of IL-4 is not robust enough to contrast ALS neurodegenerative processes.”